Efficient synthesis of N-acylbenzotriazoles using tosyl chloride: En route to suberoylanilide hydroxamic acid (SAHA)

Abstract

Various carboxylic acids were converted into N-acylbenzotriazoles (90-97 % isolated yields) via a one-pot synthesis involving activation of carboxylic acids with tosyl chloride. The novel protocol enabled stepwise manipulation of both carboxylic groups of suberic acid en route to Vorinostate (SAHA). In addition to the high yield of SAHA (84% yield over four steps) the new method comprises a simple work up and short reaction times.