反应详情

温度

0 °C

To a solution of 1-(4-fluoro-2-methoxyphenyl)-2-(3-{[(4-fluorophenyl)sulfonyl]methyl}azetidin-1-yl)ethanone (Step 2, 49.4 mg, 0.125 mmol) in dichloromethane (1 mL) at 0° C. was added boron tribromide (1M in dichloromethane, 0.5 mL, 0.5 mmol). The reaction was stirred at 0° C. for 30 minutes. Diethyl ether (5 mL) was added and the resulting slurry partitioned between saturated sodium carbonate solution and ethyl acetate. Water was added to dissolve some of the resulting precipitate and the biphasic mixture was decanted from the remaining solid. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with ethyl acetate, to give the title compound which was treated with ethereal HCl to give the hydrochloride salt (10.5 mg, 20%). 1H NMR (500 MHz, d6-DMSO) δ 11.83 (1H, s), 10.34 (1H, s), 7.95 (2H, dd, J=5.3, 8.2 Hz), 7.83 (1H, dd, J=7.3, 8.5 Hz), 7.54 (2H, t, J=8.7 Hz), 6.91 (1H, dd, J=2.0, 10.7 Hz), 6.81–6.79 (1H, m), 4.83 (2H, s), 4.19 (2H, br s), 4.05–3.97 (2H, m), 3.87–3.78 (2H, m), 3.08–3.02 (1H, m); m/z (ES+) 382 (M+H)+.

1. customthe resulting slurry partitioned between saturated sodium carbonate solution and ethyl acetate
2. additionWater was added
3. dissolutionto dissolve some of the resulting precipitate
4. customthe biphasic mixture was decanted from the remaining solid
5. extractionThe aqueous layer was extracted with ethyl acetate
6. washthe combined organic layers were washed with water and brine
7. dry with materialdried over MgSO4
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash column chromatography on silica
10. washeluting with ethyl acetate