- Patent Number:
12077,514
- Appl. No:
17/414214
- Application Filed:
December 20, 2019
- نبذة مختصرة :
The present invention relates to a method for racemizing (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid.
- Inventors:
Intervet Inc. (Madison, NJ, US)
- Assignees:
Intervet Inc. (Rahway, NJ, US)
- Claim:
1. A Method for racemizing a mixture containing (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1a) and (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1b) [chemical expression included] wherein the mixture has an enantiomeric excess of the compound according to Formula (1a) comprising the step of: (i) reacting the mixture with an alkaline compound in an organic solvent obtaining a reacted mixture wherein step (i) is carried out in the absence of phase transfer catalysts and wherein the organic solvent is 2 propanol and wherein the alkaline compound is potassium hydroxide, cesium hydroxide or potassium tert-butanolate.
- Claim:
2. The Method according to claim 1 , further comprising the steps of: (ii) acidifying the reacted mixture from step (i), to form a result mixture and (iii) separating the result mixture from step (ii) into a compound mixture and supernatant.
- Claim:
3. The Method according to claim 1 , further comprising the preceding steps of (a) reacting (5RS)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid with a compound of Formula (2A), (2B) or (2C) [chemical expression included] wherein R is an alkyl with 1 or 2 carbon atoms, [chemical expression included] wherein X is Cl or Br; in an organic solvent is 2-propanol to form a precipitate and a supernatant solution, and (b) separating the supernatant solution containing the mixture containing (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1a) and (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1b) from the precipitate.
- Claim:
4. The Method according to claim 3 , wherein in step (a) R of Formula (2A) is methyl or R of Formula (2A) is ethyl.
- Claim:
5. The Method according to claim 3 , wherein step (a) comprises heating (5RS)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]2-methyl-benzoic acid with the compound of Formula (2A), (2b) or (2C) in the solvent to an elevated temperature.
- Claim:
6. The Method according to claim 3 , wherein in step (b) the separation of the supernatant solution from step (a) from the precipitate is carried out via filtration.
- Claim:
7. The method according to claim 2 , further comprising the preceding steps of (a) reacting (5RS)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid with a compound of Formula (2A), (2B) or (2C) [chemical expression included] wherein R is an alkyl with 1 or 2 carbon atoms, [chemical expression included] wherein X is Cl or Br; in an organic solvent is 2-propanol to form a precipitate and a supernatant solution, and (b) separating the supernatant solution containing the mixture containing (5R)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1a) and (5S)-4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-benzoic acid according to Formula (1b) from the precipitate.
- Claim:
8. The method according to claim 7 , wherein in step (a) R of Formula (2A) is methyl or R of Formula (2A) is ethyl.
- Patent References Cited:
20070066617 March 2007 Mita et al.
2011051977 March 2011
2011051977 March 2011
2014090918 June 2014
- Other References:
Reichardt “Empirical Parameters of Solvent Polarity as Linear Free-Energy Relationships” Angew. Chemie Int. Ed. Engl. 1979, 18, 98-110. cited by examiner
Ceron-Carrasco, Jose P. et al, Solvent polarity scales: determination of new ET(30) values for 84 organic solvents, Journal of Physical Organic Chemistry, 2014, 512-518, 27. cited by applicant
Potapov, V.M. et al., Stereochemistry, Publishing House Moscow, 1976, 114, machine translation. cited by applicant
Potapov, V.M. et al., Stereochemistry, Publishing House Moscow, 1976, 114. cited by applicant
Sakai, Kenichi, Change in crystal habt of diastereomeric salt crystals in optical resolution using crystallization method and its utilization—Production of high optical purity 1-phenylethylamine, Journal of the Society of Organic Synthetic Chemistry, 57(5), 458-465, 1999. cited by applicant
- Primary Examiner:
O'Dell, David K
- Attorney, Agent or Firm:
Kerwick, David J.
- الرقم المعرف:
edspgr.12077514
Processing Request
No Comments.