Chemical synthesis of a chiral oxazinone

摘要

The present invention provides a process for the preparation of substantially pure N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one which comprises: (i) contacting racemic N-benzyl-3-(4-fluorophenyl)-1,4-oxazin-2-one with (-)-3-bromocamphor-8-sulphonic acid (hereinafter referred to as (-)-3-BCS) in the presence of a racemising agent; (ii) collecting the resultant crystalline (-)-3-BCS salt of N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one; and (iii) liberating the free base of N-benzyl-3-(S)-(4-fluorophenyl)-1,4-oxazin-2-one by treatment of the (-)-3-BCS salt collected in step (ii) with aqueous base.