反应详情

温度

0 °C

To a cooled (0° C.) stirred solution of 4-(adamantan-1-ylmethoxy)-5-cyclopropyl-2-fluoro-N-((2-methoxyethyl)sulfonyl)benzamide (0.30 g, 0.64 mmol) in methylene chloride (6 mL) was added a solution of boron tribromide (0.12 mL, 1.29 mmol) and 2,6-lutidine (0.15 mL, 1.29 mmol) in methylene chloride (1 mL) dropwise. The reaction mixture was stirred at 0° C. for 2 h and at ambient temperature for 1 h, then cooled to 0° C. and quenched with saturated sodium bicarbonate solution (15 mL). The mixture was diluted with methylene chloride (15 mL), layers were separated, and the aqueous layer was extracted with methylene chloride (2×15 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography eluting with a 10% to 75% gradient of ethyl acetate in hexanes to afford the title compound as colorless solid (0.07 g, 25%): 1H NMR (300 MHz, CDCl3) δ 8.71 (br. s, 1H), 7.64-7.52 (m, 1H), 6.64-6.50 (m, 1H), 4.22-4.07 (m, 2H), 3.86-3.74 (m, 2H), 3.56 (s, 2H), 2.57 (s, 1H), 2.09-1.99 (m, 4H), 1.84-1.63 (m, 12H), 1.00-0.89 (m, 2H), 0.69-0.59 (m, 2H); MS (ES+) m/z 452.3 (M+1).

1. temperaturecooled to 0° C.
2. customquenched with saturated sodium bicarbonate solution (15 mL)
3. additionThe mixture was diluted with methylene chloride (15 mL), layers
4. customwere separated
5. extractionthe aqueous layer was extracted with methylene chloride (2×15 mL)
6. washThe combined organic layers were washed with brine (20 mL)
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography
11. washeluting with a 10% to 75% gradient of ethyl acetate in hexanes