反应详情

30.1 A suspension of 37 mg NaH (55% in oil) in 2 ml DMF was treated at 0° C. under an argon atmosphere with a solution of 270 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (example 22.4). The reaction mixture was stirred for 1 hr at r.t. Then, 334 mg 2,2-difluoroethyl trifluoromethanesulfonate were added at 0° C. The reaction mixture was stirred for 2 days at r.t., then diluted with EtOAc and washed with water. The organic layer was dried over MgSO4, filtered and concentrated. The crude product was isolated by chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 9:1) to give 157 mg (3S,4S)-3-[(5-chloro-thiophene-2-carbonyl)-amino]-4-(2,2-difluoro-ethoxy)-pyrrolidine-1-carboxylic acid tert-butyl ester. Colorless solid. MS 409.0 ([M+H]+)

1. stirringThe reaction mixture was stirred for 2 days at r.t.
2. washwashed with water
3. dry with materialThe organic layer was dried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude product was isolated by chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 9:1)