1027245-89-1Relevant academic research and scientific papers
A large-scale preparation of (3S,4S)-3-(tert-butoxycarbonyl)amino-4-methylpyrrolidine and its analogs from L-aspartic acid
Yoshida, Toshihiko,Takeshita, Makoto,Orita, Hitomi,Kado, Noriyuki,Yasuda, Shingo,Kato, Hideo,Itoh, Yasuo
, p. 1128 - 1131 (2007/10/03)
(3S,4S)-3-(tert-Butoxycarbonyl)amino-4-methylpyrrolidine (12a) was synthesized from L-aspartic acid (4) on a large scale. Methylation of dimethyl (2S)-N-benzyl-N-(9-phenylfluoren-9-yl)aspartate (5), easily derived from 4, with methyl iodide gave (3R)-3-methylaspartate (6a) in 91% yield with high diastereoselectivity. Reduction of 6a with lithium aluminum hydride, followed by hydrogenolysis, protection with di-tert-butyl dicarbonate, and mesylation gave 10a in 89% overall yield. Subsequently, reaction of 10a with benzylamine under a nitrogen atmosphere at room temperature, followed by hydrogenolysis, gave the target compound (12a) in 65% overall yield. In a similar manner to that described for the preparation of 12a from 5, compound 5 was converted into 4-ethyl and 4-propyl derivatives (12b,c) in 34% and 38% overall yields.
