反应详情

温度

90 °C

A 3 L three necked flask equipped with a heating mantle, thermocouple and mechanical stirrer is charged with [7-nitro-2,3-dihydro-1,4-benzodioxin-2-yl]methyl 4-methylbenzenesulfonate (356.8 g, 0.977 mol), DMSO (1 L) and benzylamine (261.7 g, 2.44 mol). The slurry is heated to maintain an internal temperature of 90° C. Heating is continued for 18 h, and then the solution is allowed to cool to 30° C. over 2 h. Water (400 mL) is added over 15 min. then seed crystals (˜100 mg) are added resulting in rapid formation of a precipitate. The slurry is stirred for 30 min prior to additional water (2 L) being added over 1.5 h. The slurry is stirred for 4 h, the solids are collected by vacuum filtration, washed with water (2 L) and suction dried under nitrogen giving the title compound (302.87 g, 103%) as a yellow powder (94% ee). Yield is high due to trapped water, m.p. 98° C. (dried sample). LCMS (Basic Method): 2.05 min, 301 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ 7.77-7.70 (m, 1H), 7.47-7.18 (m, 6H), 7.10-7.06 (m, 1H), 4.47 (dd, J=2.5, 11.5 Hz, 1H), 4.37-4.29 (m, 1H), 4.15 (dd, J=7.1, 11.5 Hz, 1H), 3.73 (s, 2H), 2.82-2.70 (m, 2H), 2.43 (br s, 1H).

1. temperatureThe slurry is heated
2. temperatureHeating
3. temperatureto cool to 30° C. over 2 h
4. customresulting in rapid formation of a precipitate
5. stirringThe slurry is stirred for 4 h
6. filtrationthe solids are collected by vacuum filtration
7. washwashed with water (2 L) and suction
8. dry with materialdried under nitrogen giving the title compound (302.87 g, 103%) as a yellow powder (94% ee)
9. customYield
10. dry with materialis high due to trapped water, m.p. 98° C. (dried sample)
11. custom2.05 min, 301 (M+H)+