Patent ID: 7582779

Claim:
A process for preparing a compound of Formula Ia-2, having an enantiomeric purity higher than 95% enantiomeric excess and being substantially free of 15β-isomer: wherein R 2 is a single bond or a C 1-4 -alkylene or —CH 2 O—; and R 3 is a C 1-7 -alkyl or an aryl or an aralkyl, each of which is unsubstituted or substituted by a C 1-4 -alkyl, a halogen or a trihalomethyl; the process comprising the steps of: (1) reacting a compound of Formula IVa having an optical purity higher then 90% enantiomeric excess: wherein R 1 is an alkyl, an alkenyl, an alkynyl, an aryl, or an aralkyl, each of which is unsubstituted or substituted with one or more substituents selected from the group consisting of halogen, alkyl, aryl, alkoxyl, aryloxy, thioalkoxyl, thioaryloxy, alkylamino, arylamino, cyano, alkoxycarbonyl, arylcarbonyl, arylaminocarbonyl, alkylaminocarbonyl, pyridinyl, thiophenyl, furanyl, imidazolyl, morpholinyl, oxazolinyl, piperidinyl, piperazinyl, tetrahydropyranyl, pyrrolidinyl and pyrrolidinonyl; P 1 is a protecting group for the hydroxyl groups selected from the group consisting of methoxymethyl, methoxythiomethyl, 2-methoxyethoxymethyl, bis(2-chloroethoxy)methyl, tetrahydropyranyl, tetrahydrothiopyranyl, 4-methoxytetrahydropyranyl, 4-methoxytetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, triphenylmethyl, and SiR a R b R c wherein R a , R b and R c are each independently a C 1-4 alkyl, phenyl, benzyl, a substituted phenyl, or a substituted benzyl, with a cuprate derived from the compound of Formula Va-1, Formula V-2 or Formula V-3, each of which having an optical purity higher then 90% enantiomeric excess: wherein Y is a halogen, R 6 is a lower alkyl, R 2 and R 3 are as defined above, and P 2 is a protecting group for the hydroxyl groups selected from the group consisting of methoxymethyl, methoxythiomethyl, 2-methoxyethoxymethyL, bis(2-chloroethoxy)methyl, tetrahydropyranyl, tetrahydrothiopyranyl, 4-methoxytetrahydropyranyl, 4-methoxytetrahydrothiopyranyl, tetrahydrofuranyl, tetrahydrothiofuranyl, 1-ethoxyethyl, 1-methyl-1-methoxyethyl, triphenylmethyl, and SiR a R b R c wherein R a , R b and R c are each independently a C 1-4 alkyl, phenyl, benzyl, a substituted phenyl, or a substituted benzyl; to form a high optical purity compound of Formula IIa-1; (2) deprotecting the compound of Formula IIa-1 to remove P 1 and P 2 in the presence of acids to form a high optical purity compound of Formula IIa-2; (3) reducing/lactonizing the compound of Formula IIa-2, with an effective amount a reducing agent to form the high optical purity compound of Formula Ia-2; and (4) isolating the compound of Formula Ia-2 and/or Formula IIa-2 by crystallization.