Process for the preparation of atorvastatin and intermediates

Details Process for the preparation of atorvastatin and intermediates Process for the preparation of atorvastatin and intermediates

2008-08-14

2010-10-12

Kosack, Joseph R (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

Reexamination Certificate

active

07812179

ABSTRACT:
A process is provided for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 comprising:(a) reacting the aldehyde 1 with the enolate form of (S)-2-hydroxy-1,2,2-triphenylethyl acetate substituent in a chelating co-solvent;(b) hydrolysis of (R,S)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (S)-2-hydroxy-1,2,2-triphenylethyl ester (2aand 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the carboxylic acid 7;(c) treating the acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt;(d) alkylation of the (R)-7 chiral base salt or the free base derived from (R)-7, forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 and atorvastatin calcium 6,wherein R is a C1 to C6 alkyl, C6 to C9 aryl or C7 to C10 aralkyl.

REFERENCES:
patent: 4681893 (1987-07-01), Roth
patent: 5003080 (1991-03-01), Butler et al.
patent: 5273995 (1993-12-01), Roth
patent: 5298627 (1994-03-01), Butler et al.
Roth, B.D., et al., “Inhibitors of Cholesterol Biosynthesis. 3. Tetrahydro-4-hydroxy-6[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran-2-one Inhibitors of HMG-CoA Reductase. 2. Effects of Introducing Substituents at Positions Three and Four of the Pyrrole Nucleus”,J. Med. Chem., (1991), 34, 357-366.

Affiliated with

Also associated with

Rating

Process for the preparation of atorvastatin and intermediates does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Process for the preparation of atorvastatin and intermediates, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of atorvastatin and intermediates will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-4163401