1263775-13-8Relevant academic research and scientific papers
Complementary syntheses of N,O-protected-(S)-2-methylserine on a multikilogram scale
Anson, Michael S.,Clark, Hugh F.,Evans, Paul,Fox, Martin E.,Graham, Jonathan P.,Griffiths, Natalie N.,Meek, Graham,Ramsden, James A.,Roberts, Alastair J.,Simmonds, Shaun,Walker, Matthew D.,Willets, Matthew
supporting information; experimental part, p. 389 - 397 (2012/02/02)
Two complementary and scalable approaches have been used to manufacture multikilogram quantities of N,O-protected-(S)-2-methylserine. The first approach uses a diastereomeric salt resolution of 2-methylserine methyl ester as the (1S)-(+)-camphorsulfonate salt, and was used to rapidly access 15 kg of (S)-3-tert-butoxycarbonyl-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid with >99% ee. The second approach involves a stereoselective enolate methylation of a chiral cyclic l-serine derivative under cryogenic conditions. The four-step telescoped process, starting from l-serine methyl ester, was used to manufacture 20 kg of (2R,4S)-2-tert-butyl-3-tert-butoxycarbonyl-4-methyl-1,3- oxazolidine-4-carboxylic acid in 52% overall yield and 98% ee. The advantages and disadvantages for scale-up of both approaches are discussed.
