Process for preparing histone deacetylase inhibitors and intermediates thereof

Abstract

A process for preparing unsaturated esters useful as intermediates for HDAC inhibitors, by reacting an aldehyde or ketone having the following formula I: wherein Ris an aromatic group or a combined aliphatic and aromatic group; X is —O—, —S—, —COO—, —OOC—, —CONR—, or —RNCO—; Lan aliphatic linking group, an aromatic linking group, or a combined aliphatic and aromatic linking group; Rand Rare each independently hydrogen, a hydroxy group, an alkoxy group, an amino group, a carboxyl group, an amide group, an ester group, a carbamate group, an aliphatic group, an aromatic group, a combined aliphatic and aromatic group, Rand Rtogether are ═O, or one of Rand Rform a double bond with one of Rand R; Rand Rare each independently hydrogen, a hydroxy group, an alkoxy group, an amino group, a carboxy group, an amide group, an ester group, a carbamate group, an aliphatic group, an aromatic group, a combined aliphatic and aromatic group, or one of Rand Rform a double bond with one of Rand R; Ris hydrogen, an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; Ris hydrogen, an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; m is 0 or 1; n is 0 or 1; and p is 0 or 1; with an ester having the following formula II: wherein Ris an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; Rand Reach independently hydrogen, an aliphatic group, an aromatic group, a combined aliphatic and aromatic group, or one of Rand Rform a double bond with L; Rand Rare each an aliphatic group, an aromatic group, or a combined aliphatic and aromatic group; Lis an aliphatic linking group, an aromatic linking group, or a combined aliphatic and aromatic linking group; A is P or As; and p is 0 or 1.