Formamide → (3S,4R)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid amide

A solution of (3S,4R)-1-benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid methyl ester (62.82 g, 190.5 mmol) and formamide (22.7 mL, 571.4 mmol) in DMF (75 mL) was heated to 100° C. Then sodium methylate solution (5.4 M in methanol, 17.6 mL, 95.2 mmol) was added dropwise over a period of 50 min. The solution was stirred for 3 h at 100° C. (after 1 h further formamide (11.4 mL, 285.7 mmol) was added). The reaction mixture was cooled to ambient temperature and the resulting suspension was separated between ethyl acetate (1500 mL) and water (1000 mL). The organic layers were washed with brine (500 mL), combined and dried over sodium sulfate. Concentration and trituration with tert-butylmethylether (500 mL) afforded the tittle compound (51.19 g, 85%) as white crystals. MS m/e: 315.2 and 317.3 [M+H]+).

1. temperatureThe reaction mixture was cooled to ambient temperature
2. customthe resulting suspension was separated between ethyl acetate (1500 mL) and water (1000 mL)
3. washThe organic layers were washed with brine (500 mL)
4. dry with materialdried over sodium sulfate
5. concentrationConcentration and trituration with tert-butylmethylether (500 mL)

ORD 기록

ord-c3b239c9f61445969f6e3073029687a5

출처 데이터셋

uspto-grants-2016_01

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09226916B2