反应详情

Sodium hydride (60% dispersion in mineral oil, 70.7 mg, 1.06 mmol) was added to a solution of tert-butyl (3R,6S)-6-(2,3-difluorophenyl)-2-oxoazepan-3-ylcarbamate from Step E (301 mg, 0.884 mmol) in DMF (7 mL) at −35° C. After 15 min, 2,2,2-trifluoroethyl trichloromethanesulfonate (0.314 mL, 1.91 mmol) was added and stirring was continued at −35° C. After 30 min, additional sodium hydride (27 mg, 0.40 mmol) and 2,2,2-trifluoroethyl trichloromethanesulfonate (0.140 mL, 0.85 mmol) were added. After 2 h, the reaction was quenched with H2O and the mixture was extracted with EtOAc. The organic layer was washed with water (3×), then brine, then dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 70:30, to give the title compound. MS: m/z=423 (M+1).

1. customwas continued at −35° C
2. waitAfter 30 min
3. waitAfter 2 h
4. customthe reaction was quenched with H2O
5. extractionthe mixture was extracted with EtOAc
6. washThe organic layer was washed with water (3×)
7. dry with materialbrine, then dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by silica gel chromatography
11. washeluting with a gradient of hexane