Chloroacetyl chloride → (2S,4S)-1-(2-Chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile

温度

0 °C

Chloroacetyl chloride (11.13 g, 98.5 mmol) was dissolved in 120 mL of dichloromethane with stirring under argon atmosphere. Upon cooling to 0° C., (2S,4S)-4-fluoropyrrolidine-2-carbonitrile 13f (11.4 g, 75.7 mmol) was dissolved in 400 mL of dichloromethane followed by addition of triethylamine (16.1 g, 158.97 mmol). To a solution of chloroacetyl chloride in dichloromethane was added the above mentioned mixture in 30 minutes. The reaction mixture was reacted at 0° C. for 2 hours and diluted with 200 mL of ice water and 150 mL of dichloromethane. The separated organic phase was neutralized with saturated sodium bisulfate, washed with 300 mL of water and 300 mL of saturated brine successively, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (2S,4S)-1-(2-chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile 13g (8 g, yield 60%) as a white crystal.

1. customin 30 minutes
2. customThe reaction mixture was reacted at 0° C. for 2 hours
3. washwashed with 300 mL of water and 300 mL of saturated brine successively
4. dry with materialdried over anhydrous sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe resulting residue was purified by silica gel column chromatography

ORDレコード

ord-7fb06457a9b1435e9eac40f100a8c9ef

出典データセット

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08304411B2