PROCESS AND INTERMEDIATE COMPOUNDS USEFUL IN THE PREPARATION OF STATINS, PARTICULARLY ATORVASTATIN

摘要

There is provided a process for the preparation of a compound of formula (7) or salts thereof:
wherein R 1 represents an alkyl group, R 2 represents an aryl group, R 3 represents an aryl group, and X represents a group of formula -COZ, wherein Z represents -OR 4 or NR 5 R 6 which comprises
a) cyanating a compound of formula (1) to give a compound of formula (2);
b) reducing the compound of formula (2) to give a compound of formula (3);
c) coupling the compound of formula (3) with a compound of formula (4) to give a compound of formula (5);
d) when W represents -OP 2 , deprotecting and then oxidising the compound of formula (5) to give a compound of formula (6); and
e) subjecting the compound of formula (5) when W represents =O, or compound of formula (6) to ring-opening, and removal of any remaining protecting groups, to give a compound of formula (7) or salts thereof,
wherein the process comprises the further step of converting X from -COZ, wherein Z represents -OR 4 , to -COZ, wherein Z represents NR 5 R 6 , by reacting the compounds of formula (4), (5), (6) or (7) with a compound of formula HNR 5 R 6 ; and/or
wherein the process further comprises forming a compound of formuIa (2) or (3) wherein W represent =O by oxidising a compound of formula (2) or (3) when W represents -OP 2 and P 2 is hydrogen, or deprotecting and oxidising a compound of formula (2) or (3) when W represents -OP 2 and P 2 is a protecting group.