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

A suspension of 1.4 g of (2S,4S)-4-fluoropyrrolidine-2-carboxamide monohydrochloride prepared according to the similar method as that described in a patent reference (International Publication WO02/38451 pamphlet), and 3.0 ml of N,N-diisopropylethylamine in 10 ml of chloroform was added dropwise to a solution of 0.73 ml of chloroacetyl chloride in 14 ml of chloroform under cooling with an ice-water bath, and the reaction mixture was stirred for 30 minutes under cooling with an ice-water bath. Then, the reaction mixture was concentrated under reduced pressure. To a solution of the resulting residue in 14 ml of chloroform, 2.4 ml of trifluoroacetic anhydride was added dropwise under cooling with an ice-water bath. Then, the reaction mixture was allowed to room temperature, and stirred for 1 hour. This was concentrated under reduced pressure, and 0.1 M hydrochloric acid was added to the resulting residue, and this was then extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The drying agent was removed, and the solvent was removed under reduced pressure. The resulting residue was purified with silica gel column chromatography (eluent: chloroform to chloroform/methanol=30/1) to obtain 0.84 g of (2S,4S)-1-(chloroacetyl)-4-fluoropyrrolidine-2-carbonitrile.

1. customprepared
2. temperatureunder cooling with an ice-water bath
3. temperatureunder cooling with an ice-water bath
4. concentrationThen, the reaction mixture was concentrated under reduced pressure
5. additionTo a solution of the resulting residue in 14 ml of chloroform, 2.4 ml of trifluoroacetic anhydride was added dropwise
6. temperatureunder cooling with an ice-water bath
7. customwas allowed to room temperature
8. stirringstirred for 1 hour
9. concentrationThis was concentrated under reduced pressure, and 0.1 M hydrochloric acid
10. additionwas added to the resulting residue
11. extractionthis was then extracted with ethyl acetate
12. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
13. customThe drying agent was removed
14. customthe solvent was removed under reduced pressure
15. customThe resulting residue was purified with silica gel column chromatography (eluent: chloroform to chloroform/methanol=30/1)

ORD record

ord-9447f395f4f5494b8deecd9162ad7910

Source dataset

uspto-grants-2007_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07268150B2