反应详情

温度

100 °C

The product of step E (35 mg, 0.08 mmol) was dissolved in a mixture of ethylene glycol (0.5 mL) and DME (0.5 mL) then treated with 20% KOH solution (0.5 mL). The reaction mixture was heated to 100° C. for 36 h. After cooling to ambient temperature, the reaction mixture was diluted with water (5 mL) and extracted with dichloromethane (3×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by semi-preparative HPLC to give the free base which was treated directly with 1.25 M HCl in methanol solution. Concentration in vacuo afforded 7-chloro-9-(phenylsulfonyl)-2,3,4,5-tetrahydro-1H-benzofuro[2,3-d]azepine hydrochloride (5 mg, 15%, AUC HPLC>99%) as a white solid: 1H NMR (CD3OD, 300 MHz) δ 8.18 (d, J=2.0 Hz, 1H), 8.00 (d, J=7.4 Hz, 2H), 7.90 (d, J=1.7 Hz, 1H), 7.68-7.52 (m, 3H), 3.60-3.51 (m, 4H), 3.42-3.35 (m, 2H), 3.23-3.15 (m, 2H); APCI MS m/z 362 [M+H]+.

1. temperatureAfter cooling to ambient temperature
2. extractionextracted with dichloromethane (3×20 mL)
3. washThe combined organic extracts were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by semi-preparative HPLC
8. customto give the free base which
9. concentrationConcentration in vacuo