Commercial manufacturing of propofol: Simplifying the isolation process and control on related substances
A commercially viable manufacturing process for propofol (1) is described. The process avoids acid-base neutralization events during isolation of intermediate, 2,6-di-isopropylbenzoic acid (3) and crude propofol, and thus simplifies the synthesis on industrial scale to a considerable extent. Syntheses of five impurities/related substances (USP and EP) are also described.