Patent ID: 6376230
Filing Date: 2002-04-23
Classification: C07C,C07D,C07F,C12P

Abstract:
A process for the preparation of a compound of the formula: whereinG is C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, or Ar; Ar is an aromatic or heteroaromatic group or a substituted aromatic or heteroaromatic group; R3 is C1-C6 alkyl; R2a is trityl or a suitable silyl protecting group; and Ra is hydrogen, allyl or C1-C6 alkyl; or a pharmaceutically acceptable salt thereof; said process comprising the steps of: (a) contacting a compound of the formula: â€ƒwherein Rb is a suitable carboxy protecting group; and R3 is as defined above; with a cyclizing agent to form a compound of the formula: â€ƒwherein R3 is as defined above and M is hydrogen or a cation; (b) stereoselectively reducing the compound of formula (3) with a stereoselective reducing agent to yield a compound of the formula: â€ƒwherein R3 is defined as above; (c) reacting a compound of formula (4) with a hydroxy protecting agent to yield a compound of the formula: â€ƒwherein R2a is tri(C1-C6 alkyl)silyl, and R3 is as defined above; (d) reacting the compound of formula (5) with a reducing agent followed by an olefinating reagent to form a compound of the formula: â€ƒwherein G, R3 and R2a are as defined above; (e) reacting the compound of formula (6) with an oxidizing agent to provide a compound of the formula: â€ƒwherein G, R3 and R2a are as defined above; and (f) reacting the compound of formula (7) with an alkyl ester forming agent, optionally with a hydrolyzing agent to provide a compound of formula (I) and optionally forming a pharmaceutically acceptable salt thereof.