Synthesis
The general procedure for the synthesis of tert-butyl (S)-2-(cyanomethyl)pyrrolidine-1-carboxylate from the compound (CAS: 773837-37-9) and tert-butyl (S)-2-((tolylenesulfonyloxy)methyl)pyrrolidine-1-carboxylate was as follows: to a solution of dimethyl sulfoxide (255 mL) of intermediate 6 (90.4 g, 255 mmol) was added sodium cyanide ( 16.2 g, 331 mmol) and the mixture was heated to 100 °C. The reaction mixture was stirred at 100 °C for 4 h. After cooling to room temperature, the mixture was diluted with the addition of water. The aqueous layer was extracted with ethyl acetate and the organic layers were combined. The organic layer was washed sequentially with water and saturated brine and then dried over anhydrous sodium sulfate. The dried organic phase was concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography with the eluent of petroleum ether/ethyl acetate (70/30 to 30/70, v/v) to afford tert-butyl (S)-2-(cyanomethyl)pyrrolidine-1-carboxylate (35.2 g, 168 mmol, 66% yield). Mass spectrometry (ESI+) showed the molecular ion peak m/z 211 ([M+H]+, 100%).
References
[1] Patent: WO2011/111875, 2011, A1. Location in patent: Page/Page column 63-64
[2] Patent: WO2012/154676, 2012, A1. Location in patent: Page/Page column 180
[3] Patent: WO2014/71368, 2014, A1. Location in patent: Paragraph 00410
[4] Patent: WO2016/196393, 2016, A2. Location in patent: Paragraph 00277
