Process for ixabepilone, and intermediates thereof

A process for preparing an epoxide-containing azaepothilone of formula VII

• wherein RA is selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl,
• RB is selected from the group consisting of H, alkyl, and substituted or unsubstituted aryl,
• RC is selected from the group consisting of H, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and fluoroalkyl,
• the process comprising:
• a) contacting a bornane derivative of a compound of formula II
• wherein Z is selected from the group consisting of,
• and
• R1 and R2 are independently selected from the group consisting of hydrogen, triethylsilyl (TES), triisopropylsilyl (TIPS), tent-butyldimethylsilyl (TBS) and tert-butyldiphenylsilyl (TBDPS),
• with a vinyl halide of formula III
• wherein X is a halide, and R3 and R4 are independently selected from the group consisting of H, tert-butyloxycarbonyl (BOC), and tert-butylsulfonyl (SO2t-Bu), or together R3 and R4 are CPh2,
• in the presence of a transition metal catalyst to provide a compound of the formula IV
• and
• b) converting the compound of formula IV to a compound of formula V
• by converting Z to OH and converting R3 and R4 to H when one or both of R3 and R4 are other than H, wherein the converting steps are conducted in any order;
• and
• c) cyclizing the compound of formula V to the compound of formula VI
• d) treating a compound of formula VI with an epoxidizing agent to form a compound of formula VIII
• and
• e) deprotecting the compound of formula VIII to provide the epoxide containing azaepothilone VII.