Process and intermediate compounds useful in the preparation of statins, particularly rosuvastatin

摘要

There is provided a process for the preparation of a compound of formula (7): formula (7) wherein R¹ represents an alkyl group, R² represents an aryl group, R³ represents hydrogen, a protecting group or an alkyl group; and R⁴ represents hydrogen, a protecting group or a SO₂R⁵ group where R⁶ is an alkyl group, which comprises
a) hydroxylating a compound of formula (1): formula (1) wherein Y represents a halo group, P¹ represents hydrogen or a protecting group, and W represents =O or -OP², in which P² represents hydrogen or a protecting group, to give a compound of formula (2): formula (2) b) oxidising the compound of formula (2) to give a compound of formula (3): formula (3) c) coupling the compound of formula (3) with a compound of formula (4): formula (4) wherein R³ represents a protecting group or an alkyl group, R⁴ represents a protecting group or a SO₂R⁵ group where R⁵ is an alkyl group; and R⁶ represents (PR⁷R⁸)+X^- or P (=O)R⁷R⁸ in which X is an anion and R⁷ and R⁸ each independently is an alkyl, aryl, alkoxy or aryloxy group, to give a compound of formula (5): formula (5) wherein R³ represents a protecting group or an alkyl group; and R4 represents a protecting group or a SO₂R⁵ group where R⁵ is an alkyl group, d) when W represents -OP², removing any P² protecting group and oxidising the compound of formula (5) to give a compound of formula (6): formula (6) and e) subjecting the compound of formula (5) when W represents =O, or compound of formula (6) to ring-opening, removal of any P¹ protecting groups, and optionally removing any additional protecting groups to give a compound of formula (7).