Both Enantiomers of N-Boc-indoline-2-carboxylic Esters

• Published in: Bulletin of the Chemical Society of Japan
• Main Authors: Kurokawa, Masayuki, Sugai, Takeshi
• Format: Article in Journal/Newspaper
• Language: English
• Published: Oxford University Press (OUP) 2004
• Subjects: Antarc*; Antarctica
• Online Access: http://dx.doi.org/10.1246/bcsj.77.1021; https://academic.oup.com/bcsj/article-pdf/77/5/1021/56264213/bcsj.77.1021.pdf

Abstract An immobilized form of Candida antarctica lipase (Chirazyme L-2) catalyzed enantioselective hydrolysis (E > 1000) of N-Boc-indoline-2-carboxylic acid methyl ester. The reaction proceeded efficiently at 60 °C, a temperature over the melting point of substrate, in the conversion of 49.9% to provide the hydrolyzed product, (S)-carboxylic acid with >99.9% ee and the unreacted (R)-ester with 99.6% ee. A newly developed expeditious route to the racemic substrate (a total of six steps, 60% yield), starting from aniline and ethyl α-methylacetoacetate, established the scalable chemo-enzymatic synthesis of the desired compounds in both enantiomerically pure forms.