Processes and intermediates for the preparation of carbaprostacyclin analogues

A process for preparing a compound of Formula (R)-1 enriched in the (R)-enantiomer and having an optical purity of at least 95% enantiomeric excess,

• wherein Y is —CH2OP or -COOR1;
• X is F, Cl, Br, I, or —OTs;
• P is H or a hydroxyl protective group;
• and R1 is C1-7-alkyl, aryl or aralkyl, each of which is unsubstituted or substituted by C1-4-alkyl, C2-7-alkenyl, C2-7-alkynyl, nitro, halogen or alkoxy, the process comprising the steps of:
• (1) enantioselectively (R)-esterifying a compound of Formula 1:
• wherein Y and X are as defined above, with an acyl donor of Formula D:
• wherein R4 and R5 are independently H or C1-6 alkyl, and a first lipase, to form a (R)-ester of Formula (R)-1b′ and an unreacted (S)-alcohol of Formula (S)-1:
• (2) removing the unreacted (S)-alcohol;
• and
• (3) deacylating the resultant (R)-ester.

A process for preparing a compound of Formula (R)-1d enriched in the (R)-enantiomer and having an optical purity of at least 95% enantiomeric excess,

• wherein X is F, Cl, Br, I, or —OTs;
• and R
• 4 is H or C1-6 alkyl, the process comprising the steps of:
• (1) enantioselectively (R)-esterifying the compound of claim 37 with an acyl donor of Formula D:
• wherein R4 and R5 are independently H or C1-6 alkyl, and a first lipase, to form a mixture of a compound of Formula (R)-1d and a compound of Formula (S)-1e:
• (2) removing the compound of Formula (S)-1e.