反应详情

A solution of hydrogen chloride in dioxane (4.0 M, 10 mL, 41 mmol) was added to tert-butyl {5-[(4aR,6R,8aS)-2-(benzoylamino)-6-(fluoromethyl)-4,4a,5,6-tetrahydropyrano[3,4-d][1,3]thiazin-8a(8H)-yl]-2,4-difluorobenzyl}carbamate (C25) (0.8277 g, 1.506 mmol) at room temperature. The reaction mixture was stirred overnight and then concentrated under reduced pressure to yield a brown solid. The solid was partitioned between a 1:1 solution of ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate (100 mL). The organics were separated and the aqueous layer was extracted further with ethyl acetate (2×100 mL). The combined organics were then washed with brine (200 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure to yield the product as a brown solid (0.598 g), which was taken directly to the following step. LCMS m/z 450 [M+H+]. 1H NMR (400 MHz, CD3OD), characteristic peaks: δ 8.11-8.13 (m, 2H), 7.44-7.57 (m, 3H), 7.09 (dd, J=12.3, 9.6 Hz, 1H), 4.49-4.51 (m, 1H), 4.37-4.39 (m, 1H), 3.20-3.23 (m, 1H), 3.01 (dd, J=13.0, 4.2 Hz, 1H), 2.77 (dd, J=13.0, 2.8 Hz, 1H), 1.89 (m, 1H), 1.70 (ddd, J=13.4, 4.1, 2.2 Hz, 1H).

1. concentrationconcentrated under reduced pressure
2. customto yield a brown solid
3. customThe solid was partitioned between a 1:1 solution of ethyl acetate (100 mL) and saturated aqueous sodium bicarbonate (100 mL)
4. customThe organics were separated
5. extractionthe aqueous layer was extracted further with ethyl acetate (2×100 mL)
6. washThe combined organics were then washed with brine (200 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure