+

US20070055066A1 - Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol - Google Patents

Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol Download PDF

Info

Publication number
US20070055066A1
US20070055066A1 US11/514,741 US51474106A US2007055066A1 US 20070055066 A1 US20070055066 A1 US 20070055066A1 US 51474106 A US51474106 A US 51474106A US 2007055066 A1 US2007055066 A1 US 2007055066A1
Authority
US
United States
Prior art keywords
compound
formula
phenyl
alkyl
oxazolidine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/514,741
Other languages
English (en)
Inventor
James Towson
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme Holdings Pty Ltd
Intervet Inc
Original Assignee
Schering Plough Animal Health Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering Plough Animal Health Corp filed Critical Schering Plough Animal Health Corp
Priority to US11/514,741 priority Critical patent/US20070055066A1/en
Assigned to SCHERING-PLOUGH PTY. LIMITED, SCHERING-PLOUGH LTD., SCHERING-PLOUGH ANIMAL HEALTH CORPORATION reassignment SCHERING-PLOUGH PTY. LIMITED ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: TOWSON, JAMES C.
Publication of US20070055066A1 publication Critical patent/US20070055066A1/en
Abandoned legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/44—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
    • C07C317/48—Sulfones; Sulfoxides having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being part of nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C07C315/04—Preparation of sulfones; Preparation of sulfoxides by reactions not involving the formation of sulfone or sulfoxide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C315/00—Preparation of sulfones; Preparation of sulfoxides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/04—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D263/06—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by oxygen atoms, attached to ring carbon atoms

Definitions

  • the present invention relates generally to a new process for preparing oxazolidine protected aminodiol compounds. These compounds are useful intermediates in the process for making Florfenicol.
  • Florfenicol is a broad spectrum antibiotic of Formula I
  • Florfenicol is also known as [R-(R*,S*)]-2,2-Dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl]acetamide.
  • the present invention addresses this shortcoming and provides a still further alternative method of preparing useful intermediates included in the synthesis of Florfenicol.
  • the present invention includes a process for preparing an oxazolidine protected aminodiol compound of Formula V:
  • R 1 is hydrogen, methylthio, methylsulfoxy, methylsulfonyl, fluoromethylthio, fluoromethylsulfoxy, fluoromethylsulfonyl, nitro, fluoro, bromo, chloro, acetyl, benzyl, phenyl, halo substituted phenyl, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, or C 2-6 heterocyclic group;
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, aryl, or C 2-6 heterocyclic group;
  • R 3 is hydrogen, C 1-6 alkyl, C 0-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, aryl or C 2-6 heterocyclic group; and
  • R 4 is hydrogen, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, benzyl, phenyl or C 1-6 phenylalkyl group, where the phenyl ring may be substituted by one or two halogens, C 1-6 alkyl, or C 1-6 alkoxy.
  • the process includes the steps of:
  • R 1 is as defined above and R 5 is hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, benzyl, phenyl or C 1-6 phenylalkyl, in a vessel with a reducing agent in an alcoholic solvent to form an aminodiol compound of Formula VII:
  • R 1 is as defined above;
  • R 1 , R 2 and R 3 are as defined above;
  • esters of Formulas IV and VI generates the expensive free base starting material of Formula III in situ, thereby eliminating the need to isolate this difficult to isolate compound. Yield losses for the free base starting material of Formula III due to isolation are thus eliminated with resulting increased yield and lower cost for the oxazolidine protected aminodiol compound of Formula V, or specifically the compound of Formula II.
  • the present invention thus has the advantage of being an efficient and economical process for preparing Florfenicol, its analogs and oxazolidine intermediates related thereto.
  • alcoholic solvent includes C 1 to C 10 alcohols such as methanol and ethanol and mixtures thereof, C 2 to C 10 dialcohols such as ethylene glycol and C 1 to C 10 trialcohols such as glycerin.
  • the alcoholic solvent can be admixed with any suitable cosolvent.
  • Such cosolvents can include other solvents which are miscible with the alcoholic solvent such as C 4 to C 10 alkanes, aromatic solvents such as benzene, toluene, xylenes, halobenzenes such as chlorobenzene, and ethers such as diethylether, tert-butylmethylether, isopropylether and tetrahydrofuran, or mixtures of any of the above solvents or cosolvents.
  • alcoholic solvent such as C 4 to C 10 alkanes
  • aromatic solvents such as benzene, toluene, xylenes
  • halobenzenes such as chlorobenzene
  • ethers such as diethylether, tert-butylmethylether, isopropylether and tetrahydrofuran, or mixtures of any of the above solvents or cosolvents.
  • alkyl means a straight or branched alkyl such as methyl, ethyl, propyl, or sec-butyl. Alternatively, the number of carbons in alkyl may be specified.
  • C 1 to C 6 alkyl means an “alkyl” as described above containing 1 to 6 carbon atoms.
  • Haloalkyl means an “alkyl” as described above wherein one or more hydrogens are replaced by halo.
  • aryl means phenyl, or phenyl substituted by C 1 to C 6 alkyl or halo.
  • Substituted benzyl means benzyl substituted by C 1 to C 6 alkyl or halo.
  • halo means fluoro, chloro, bromo or iodo.
  • halo aryl means phenyl substituted by halo.
  • R 1 is hydrogen, methylthio, methylsulfoxy, methylsulfonyl, fluoromethylthio, fluoromethylsulfoxy, fluoromethylsulfonyl, nitro, fluoro, bromo, chloro, acetyl, benzyl, phenyl, halo substituted phenyl, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, or C 2-6 heterocyclic group;
  • R 2 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, aryl, or C 2-6 heterocyclic group;
  • R 3 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, aryl or C 2-6 heterocyclic group; and
  • R 4 is hydrogen, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, benzyl, phenyl or C 1-6 phenylalkyl group, where the phenyl ring may be substituted by one or two halogens, C 1-6 alkyl or C 1-6 alkoxy.
  • the compounds corresponding thereto are useful intermediates in the formation of Florfenicol and related compounds.
  • One preferred process corresponding to the invention includes the steps of:
  • R 1 is as defined above and R 5 is hydrogen, C 1-6 alkyl, C 3-8 cycloalkyl, benzyl, phenyl or C 1-6 alkylphenyl, in a vessel with a reducing agent in an alcoholic solvent to form an aminodiol compound of Formula VII:
  • R 1 is as defined above;
  • R 1 , R 2 and R 3 are as defined above;
  • R 1 is methylthio, methylsulfoxy, or methylsulfonyl. More preferably, R 1 is methylsulfonyl;
  • R 2 and R 3 are hydrogen, methyl, ethyl or propyl. More preferably, R 2 and R 3 are methyl;
  • R 4 is a methyl, ethyl, propyl or isopropyl group. More preferably, R 4 is methyl; and
  • R 5 is methyl, ethyl, n-propyl, isopropyl, butyl, t-butyl, or pentyl.
  • the compound of Formula IV is commercially available.
  • Alternative compounds corresponding to Formula VI can be prepared using standard organic synthetic techniques without undue experimentation.
  • ester compound of Formula VI is N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl-N-(2-aminoethyl)-2-aminoethyl
  • esters correspond to:
  • R 5 is as defined above.
  • the compound corresponding to Formula VI is the compound of Formula IV.
  • reaction vessel shall be understood to mean a container known to those of ordinary skill which is capable of holding the reactants and allowing the reaction step to proceed to completion.
  • the size and type of vessel will, of course, depend upon the size of the batch and the specific reactants selected.
  • suitable reducing agents can be employed in carrying out the process of the invention.
  • suitable reducing agents include NaBH 4 , KBH 4 , Ca(BH 4 ) 2 , and LiBH 4 and mixtures thereof when an alcoholic solvent is used.
  • the alcoholic solvent can also be one of many art-recognized solvents but some preferred solvents include methanol, ethanol, propanol, isopropanol, butanol and pentanol and mixtures thereof.
  • One preferred reducing agent is KBH 4 .
  • the molar ratio of reducing agent, such as KBH 4 , to the compound of Formula IV is between about 1:1 and about 2:1.
  • the reducing agent is KBH 4
  • the molar ratio of KBH 4 to the compound of Formula IV is about 1.5:1 and the preferred solvent is methanol.
  • This reduction can be carried out at a temperature of about 30° C. to about 80° C. in about 8 hours.
  • the temperature is below 60° C. and the time for the reaction to reach completion is under 6 hours.
  • the artisan can use reducing agents such as LiAlH 4 or NaAlH 4 when anhydrous conditions are desired.
  • solvents like ether or tetrahydrofuran can be used.
  • aminodiol compound corresponding to Formula VII is reacted, preferably in the same vessel (i.e., in situ), with an oxazolidine forming reagent such as formaldehyde, acetone, 2-methoxypropene, 2,2-dimethoxypropane, 2,2-diethoxypropane and mixtures thereof, under conditions such as those set forth in the examples to make a compound of Formula VIII.
  • an oxazolidine forming reagent such as formaldehyde, acetone, 2-methoxypropene, 2,2-dimethoxypropane, 2,2-diethoxypropane and mixtures thereof.
  • the compound corresponding to Formula VIII is the compound:
  • the methanol solvent is removed by distillation and replaced with another solvent designated herein as an oxazolidine forming solvent such as toluene, xylene, hexane or a mixture thereof.
  • the preferred oxazolidine forming solvent is toluene.
  • the ratio of the oxazolidine forming solvent to methanol is about 0.5:1 to 3:1 with the preferred ratio of about 1:1.
  • An oxazolidine forming reagent such as formaldehyde, acetone, 2-methoxypropene, 2,2-dimethoxypropane, 2,2-diethoxypropane and mixtures thereof is then added.
  • One preferred oxazolidine forming reagent is acetone which is added in a ratio to toluene of about 0.5:1 to 3:1 with the preferred ratio of about 1:1.
  • the reaction runs to completion to form the oxazolidine compound of Formula VIII over about 12-18 hours in the presence of a base designated herein as an oxazolidine promoting base such as potassium carbonate, sodium carbonate, trimethylamine or triethylamine.
  • a preferred base is potassium carbonate or triethylamine.
  • the oxazolidine forming reaction can be carried out at a temperature of about 65-85° C.
  • the compound of Formula VIII remain in the same vessel after completion of the reaction step when the first N-acylating agent is added.
  • first and second are used for describing the N-acylating (first) agents so as to distinguish the agents used for making the oxazolidine protected aminodiol compounds of Formula V from the N-acylating agents (second) which are used in the formation of the compounds of Formula XI after the intermediate of Formula X has been formed.
  • some preferred first N-acylating compounds are of the formula R 6 COR 4
  • R 4 is hydrogen, OH, C 1-6 alkyl, C 1-6 haloalkyl, C 3-8 cycloalkyl, benzyl, phenyl or C 1-6 phenylalkyl group, where the phenyl ring may be substituted by one or two halogens, C 1-6 alkyl or C 1-6 alkoxy; and
  • R 6 is halo, or C 1-6 alkoxy.
  • Some more preferred first acylating agents include acetyl chloride, acetyl bromide, propionyl chloride, propionyl bromide, butyl chloride, methyl chloroformate, ethyl chloroformate, propyl chloroformate and mixtures thereof.
  • the compound corresponding to Formula V is the compound:
  • a base such as potassium carbonate, sodium carbonate, trimethylamine or triethylamine is added in a molar equivalent ratio to the compound of Formula VII of about 1:1 to 1:3.
  • the preferred base is potassium carbonate or triethylamine and the preferred molar equivalent ratio is about 1.1 to 1.
  • the preferred first N-acylating agent acetyl chloride is added in a molar ratio to the compound of Formula VII of about 1:1 to 3:1 with the preferred ratio being 1.1:1.
  • Reaction temperature is about 20-30° C. and the reaction completes in about 2-4 hours.
  • R 1 , R 2 , R 3 and R 4 are as defined above.
  • Suitable fluorinating agents include, without limitation, N-(2-chloro-1,1,2-trifluoroethyl)diethylamine, N-(2-chloro-1,1,2-trifluoroethyl)dimethylamine, N-(2-chloro-1,1,2-trifluoroethyl)dipropylamine, N-(2-chloro-1,1,2-trifluoroethyl)pyrrolidine, N-(2-chloro-1,1,2-trifluoroethyl)-2-methylpyrrolidine, N-(2-chloro-1,1,2-trifluoroethyl)-4-methylpiperazine, N-(2-chloro-1,1,2-trifluoroethyl)morpholine, N-(2-chloro-1,1,2-trifluoroethyl)piperidine, 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine, (Diethylamino)sulfurtrifluor
  • the molar ratio of the fluorinating agent such as N,N-diethyl-1,1,2,3,3,3-hexafluoro-1-propanamine to the compound according to Formula V is between about 1:1 and about 2:1.
  • the molar ratio of the N,N-diethyl-1,1,2,3,3,3-hexafluoro-1-propanamine to the compound of Formula V is about 1.5:1.
  • the fluorinating step can be carried out at a temperature of from about 80° C. to about 110° C. and at a pressure of about 60 psi.
  • the organic solvent used during the fluorinating step is preferably 1,2-dichloroethane, methylene chloride, chloroform, chlorobenzene, chlorinated hydrocarbons or mixtures thereof.
  • a more preferred organic solvent is methylene chloride.
  • R 1 is as defined above.
  • R 1 is CH 3 SO 2 .
  • the acid used in this part of the process can be an inorganic acid like aqueous hydrochloric acid, sulfuric acid, or phosphoric acid or an organic acid like methanesulfonic acid.
  • the hydrolyzing step is preferably carried out by heating the compound of Formula IX with 6N aqueous hydrochloric acid at a temperature of from about 90° C. to about 105° C. for about 60 minutes. Other suitable hydrolyzing steps will be apparent to those of ordinary skill.
  • R 1 is the same as above, preferably CH 3 SO 2 ;
  • R 7 is hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 dihaloalkyl, C 1-6 trihaloalkyl, C 3-8 cycloalkyl, C 3-8 cyclohaloalkyl, C 3-8 cyclodihaloalkyl, C 3-8 cyclotrihaloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 aralkyl, C 2-6 aralkenyl, C 2-6 heterocyclic benzyl, phenyl or phenyl alkyl where the phenyl ring may be substituted by one or two halogens, C 1-6 alkyl or C 1-6 alkoxy.
  • R 7 is CH 2 Cl, CHCl 2 , CCl 3 , CH 2 Br, CHBr 2 , CBr 3 , CH 2 F, CHF 2 , or CF 3 .
  • one preferred compound of Formula XI is:
  • R 7 is as defined above.
  • the compound corresponding to Formula XI is the compound of Formula I:
  • Suitable second N-acylating compounds are of the formula R 8 COR 7 , wherein R 7 is the same as that described above and R 8 is OH, halo or C 1-6 alkoxy.
  • Some more preferred second N-acylating agents include dichloroacetic acid or a reactive derivative thereof.
  • a non-limiting list includes reagents such as methyldichloroacetate, ethyldichloroacetate, or dichloroacetylchloride.
  • the second N-acylation step is preferably carried out by reacting the compound of Formula X in methanol with methyldichloroacetate at a temperature of from about 20° C. to about 30° C. for about 12 hours.
  • the compound of Formula XI can optionally be purified by heating in a mixture of an alkyl mono, di or tri alcohol and water.
  • the alcohols in this part of the process can be C 1-10 monoalcohols, C 1-10 dialcohols and C 1-10 trialcohols and mixtures thereof.
  • a non-limiting list of the C 1-10 monoalcohols includes methanol, ethanol, propanol, isopropanol, butanol, sec-butanol, t-butanol and pentanol.
  • One preferred C 1-10 monoalcohol is isopropanol.
  • C 1-10 dialcohols includes ethylene glycol, propylene glycol and butylene glycol of which propylene glycol is preferred. Glycerin is the preferred C 1-10 trialcohol. A C 1-10 monoalcohol is preferred for the purification. One most preferred C 1-10 monoalcohol is isopropanol.
  • the ratio of alcohol, such as isopropanol, to water is between 1:5 and 5:1.
  • the ratio of isopropanol to water is 1:1.
  • the compound of Formula XI is dissolved in a 1:1 mixture of isopropanol and water heated to the reflux point of the mixture.
  • the solution is clarified by filtration with active carbon and a filter aid, then cooled to about 10-30° C. and the purified compound of Formula XI crystallizes from solution.
  • the solution is cooled to about 20-25° C. and the purified compound of Formula XI crystallizes from solution.
  • the purified compound corresponding to Formula XI is the compound of Formula I.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
US11/514,741 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol Abandoned US20070055066A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US11/514,741 US20070055066A1 (en) 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US71468505P 2005-09-07 2005-09-07
US11/514,741 US20070055066A1 (en) 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol

Publications (1)

Publication Number Publication Date
US20070055066A1 true US20070055066A1 (en) 2007-03-08

Family

ID=37684114

Family Applications (3)

Application Number Title Priority Date Filing Date
US11/515,278 Abandoned US20070055067A1 (en) 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to Florfenicol
US11/514,741 Abandoned US20070055066A1 (en) 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol
US11/515,135 Active 2029-01-11 US7786329B2 (en) 2005-09-07 2006-08-31 Process for preparing ester oxazolidine compounds and their conversion to Florfenicol

Family Applications Before (1)

Application Number Title Priority Date Filing Date
US11/515,278 Abandoned US20070055067A1 (en) 2005-09-07 2006-08-31 Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to Florfenicol

Family Applications After (1)

Application Number Title Priority Date Filing Date
US11/515,135 Active 2029-01-11 US7786329B2 (en) 2005-09-07 2006-08-31 Process for preparing ester oxazolidine compounds and their conversion to Florfenicol

Country Status (19)

Country Link
US (3) US20070055067A1 (fr)
EP (3) EP1928820B1 (fr)
JP (3) JP2009507842A (fr)
KR (3) KR20080049040A (fr)
CN (3) CN101300237A (fr)
AU (3) AU2006287697A1 (fr)
BR (3) BRPI0615767A2 (fr)
CA (3) CA2621961A1 (fr)
EC (3) ECSP088268A (fr)
ES (1) ES2459205T3 (fr)
IL (3) IL189829A0 (fr)
MX (3) MX2008003188A (fr)
NO (3) NO20081684L (fr)
RU (3) RU2008112946A (fr)
SI (1) SI1928820T1 (fr)
TW (3) TW200800924A (fr)
UA (1) UA93212C2 (fr)
WO (3) WO2007030385A2 (fr)
ZA (3) ZA200802046B (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040242546A1 (en) * 2003-05-29 2004-12-02 Schering-Plough Animal Health Corporation Compositions and method for treating infection in cattle and swine
US20080146640A1 (en) * 2006-12-13 2008-06-19 Glinka Tomasz W Water-Soluble Prodrugs of Chloramphenicol, Thiamphenicol, and Analogs Thereof
US20090149657A1 (en) * 2005-11-09 2009-06-11 Krka Process for the synthesis of intermediates of chloramphenicol or its analogues
US20110166359A1 (en) * 2008-07-30 2011-07-07 Paquette Leo A Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BRPI0814581A2 (pt) * 2007-07-25 2017-05-09 Intervet Int Bv processo para a preparação de um composto, e, composto.
US20090170954A1 (en) * 2007-12-14 2009-07-02 Schering-Plough Ltd. Process for Recovering Florfenicol and Florfenicol Analogs
CN101941927B (zh) * 2010-09-28 2012-10-03 湖北美天生物科技有限公司 氟苯尼考中间体(1r,2r)-2-氨基-1–(4-(甲砜基)苯基)-1,3-丙二醇的合成方法
AU2012251438A1 (en) 2011-05-02 2013-11-14 Pfizer Inc. Novel cephalosporins useful as antibacterial agents
CN103254103A (zh) * 2013-06-05 2013-08-21 南通金利油脂工业有限公司 氟化剂在制备氟苯尼考工艺中的应用
CN103965085B (zh) * 2014-04-17 2016-02-24 上海恒晟药业有限公司 一种取代1,2-氨基醇药物的制备方法
CN106278964B (zh) * 2016-07-31 2018-01-16 浙江润康药业有限公司 氟苯尼考的制备方法
CN111500652B (zh) * 2019-01-30 2024-03-26 苏州引航生物科技有限公司 一种制备氟苯尼考的方法
CN110302163A (zh) * 2019-07-23 2019-10-08 东莞正大康地饲料有限公司 一种氟苯尼考可溶性粉及其制备方法
CN110773207A (zh) * 2019-09-25 2020-02-11 陈红菊 一种在室温且无光条件下可完全分解甲醛的冷触媒材料及其制备方法
CN111423391A (zh) * 2020-03-18 2020-07-17 浙江康牧药业有限公司 一种氟苯尼考中间体的制备方法
CN113402475A (zh) * 2021-06-07 2021-09-17 山东国邦药业有限公司 一种氟苯尼考中间体的制备方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5663361A (en) * 1996-08-19 1997-09-02 Schering Corporation Process for preparing intermediates to florfenicol
US7126005B2 (en) * 2003-10-06 2006-10-24 Aurobindo Pharma Limited Process for preparing florfenicol

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4002637A (en) * 1973-07-09 1977-01-11 Rohm And Haas Company Oxazolidine, oxazolidine-containing condensation and addition polymers and methods of producing them
EP0677511A3 (fr) * 1983-06-02 1996-07-24 Zambon Spa Intermédiaires pour la préparation des dérivés de 1-phényl-1-hydroxy-2-amino-3-fluoropropane.
IT1237798B (it) * 1989-10-20 1993-06-17 Zambon Spa Processo per l'inversione stereochimica di (2s,3s)-2-ammino-3-fenil-1 ,3-propandioli nei corrispondenti enantiomeri (2r,3r).
CA2142883A1 (fr) * 1992-08-21 1994-03-03 Saizo Shibata Compose de dioxacycloalkane ayant une activite inhibitrice de la renine
JP2001240571A (ja) * 2000-03-01 2001-09-04 Udagawa Reiko フッ素アルコールの製造方法
EP1487785A2 (fr) * 2002-03-08 2004-12-22 Schering-Plough Ltd. Antibiotiques de type florfenicol

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5663361A (en) * 1996-08-19 1997-09-02 Schering Corporation Process for preparing intermediates to florfenicol
US7126005B2 (en) * 2003-10-06 2006-10-24 Aurobindo Pharma Limited Process for preparing florfenicol

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040242546A1 (en) * 2003-05-29 2004-12-02 Schering-Plough Animal Health Corporation Compositions and method for treating infection in cattle and swine
US8034845B2 (en) 2003-05-29 2011-10-11 Intervet Inc. Compositions and method for treating infection in cattle and swine
US9084719B2 (en) 2003-05-29 2015-07-21 Intervet Inc. Compositions and method for treating infection in cattle and swine
US20090149657A1 (en) * 2005-11-09 2009-06-11 Krka Process for the synthesis of intermediates of chloramphenicol or its analogues
US20080146640A1 (en) * 2006-12-13 2008-06-19 Glinka Tomasz W Water-Soluble Prodrugs of Chloramphenicol, Thiamphenicol, and Analogs Thereof
US8044230B2 (en) 2006-12-13 2011-10-25 Intervet Inc. Water-soluble prodrugs of chloramphenicol, thiamphenicol, and analogs thereof
US20110166359A1 (en) * 2008-07-30 2011-07-07 Paquette Leo A Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol
US8314252B2 (en) 2008-07-30 2012-11-20 Intervet Inc. Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol

Also Published As

Publication number Publication date
ZA200802046B (en) 2008-12-31
IL189828A0 (en) 2008-11-03
BRPI0615767A2 (pt) 2011-05-24
CA2621961A1 (fr) 2007-03-15
KR20080041699A (ko) 2008-05-13
KR101408596B1 (ko) 2014-06-17
BRPI0615764A2 (pt) 2011-05-24
RU2008112952A (ru) 2009-10-20
EP1928820B1 (fr) 2014-01-29
AU2006287696A1 (en) 2007-03-15
RU2008112950A (ru) 2009-10-20
WO2007030405A2 (fr) 2007-03-15
CA2621971A1 (fr) 2007-03-15
TW200800924A (en) 2008-01-01
KR20080049040A (ko) 2008-06-03
TW200804254A (en) 2008-01-16
UA93212C2 (ru) 2011-01-25
JP2009507842A (ja) 2009-02-26
EP1934190A2 (fr) 2008-06-25
WO2007030385A3 (fr) 2007-05-24
CN101300238A (zh) 2008-11-05
US20070055067A1 (en) 2007-03-08
US7786329B2 (en) 2010-08-31
AU2006287697A1 (en) 2007-03-15
KR20080049039A (ko) 2008-06-03
ECSP088267A (es) 2008-04-28
AU2006287716A1 (en) 2007-03-15
ES2459205T3 (es) 2014-05-08
SI1928820T1 (sl) 2014-08-29
NO20081685L (no) 2008-06-05
WO2007030386A3 (fr) 2007-05-24
CA2621987A1 (fr) 2007-03-15
CN101300227B (zh) 2013-07-03
JP5113754B2 (ja) 2013-01-09
WO2007030386A2 (fr) 2007-03-15
TW200804253A (en) 2008-01-16
WO2007030385A2 (fr) 2007-03-15
JP2009507074A (ja) 2009-02-19
ZA200802048B (en) 2008-11-26
JP2009507075A (ja) 2009-02-19
ECSP088268A (es) 2008-04-28
IL189830A0 (en) 2008-11-03
CN101300227A (zh) 2008-11-05
US20070055080A1 (en) 2007-03-08
MX2008003188A (es) 2008-03-18
RU2008112946A (ru) 2009-10-20
WO2007030405A3 (fr) 2007-05-18
ZA200802047B (en) 2008-12-31
CN101300237A (zh) 2008-11-05
TWI331139B (en) 2010-10-01
NO20081684L (no) 2008-06-05
ECSP088266A (es) 2008-04-28
BRPI0615565A2 (pt) 2011-05-24
EP1934189A2 (fr) 2008-06-25
MX2008003186A (es) 2008-03-18
MX2008003187A (es) 2008-03-18
NO20081686L (no) 2008-06-05
EP1928820A2 (fr) 2008-06-11
IL189829A0 (en) 2008-11-03

Similar Documents

Publication Publication Date Title
US20070055066A1 (en) Process for preparing oxazolidine protected aminodiol compounds useful as intermediates to florfenicol
US20080319200A1 (en) Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol
US8314252B2 (en) Process for preparing oxazoline-protected aminodiol compounds useful as intermediates to florfenicol
US7126005B2 (en) Process for preparing florfenicol
US20100210851A1 (en) Process for preparing oxazolidine- and oxazolidinone-aminodiols
US8115019B2 (en) Cis-2, 6-disubstituted tetrahydropyran derivatives and preparation method thereof

Legal Events

Date Code Title Description
AS Assignment

Owner name: SCHERING-PLOUGH ANIMAL HEALTH CORPORATION, NEW JER

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:TOWSON, JAMES C.;REEL/FRAME:018365/0761

Effective date: 20060911

Owner name: SCHERING-PLOUGH PTY. LIMITED, AUSTRALIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:TOWSON, JAMES C.;REEL/FRAME:018365/0761

Effective date: 20060911

Owner name: SCHERING-PLOUGH LTD., SWITZERLAND

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:TOWSON, JAMES C.;REEL/FRAME:018365/0761

Effective date: 20060911

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载