反应详情

温度

45 °C

A mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-ethyl)pyridine 1-oxide (Int. 6) (424 mg, 0.607 mmol) and tin(II) chloride dihydrate (548 mg, 2.428 mmol) in THF (40 ml) was heated at 45° C. for 2 hours. Additional tin(II) chloride dihydrate (1.644 g, 7.284 mmol) was added in 3 portion over 3 hours at 60° C., and the resulting mixture was heated to reflux overnight. The solvent was removed and the mixture was diluted with ethyl acetate; aqueous sat. NaHCO3 was added and the mixture was filtered through a celite pad. The filtered phases were separated and the organic layer was washed with brine and dried over sodium sulfate; the solvent was removed and the crude was purified by flash chromatography on silica gel column (DCM/MeOH=98/2) affording (S)-4-(2-(1-(4-aminophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)ethyl)-3,5-dichloropyridine 1-oxide (Int. 7) (207 mg, 0.310 mmol, MS/ESI+667.96 [MH]+, [αD]=−61.24, c=1, DCM).

1. temperaturethe resulting mixture was heated
2. temperatureto reflux overnight
3. customThe solvent was removed
4. additionthe mixture was diluted with ethyl acetate
5. additionaqueous sat. NaHCO3 was added
6. filtrationthe mixture was filtered through a celite pad
7. customThe filtered phases were separated
8. washthe organic layer was washed with brine
9. dry with materialdried over sodium sulfate
10. customthe solvent was removed
11. customthe crude was purified by flash chromatography on silica gel column (DCM/MeOH=98/2)