反应详情

温度

65 °C

To (9aS)-8-(phenylmethyl)hexahydropyrazino[2,1-c][1,4]oxazine-6,7-dione (2.06 g, 7.90 mmol) in THF (20 mL) at 0° C. was added LAH (30.0 mL, 29.6 mmol, 1M in THF) dropwise. The solution was heated overnight at 45° C. and a subsequent 5 days at 65° C. The reaction was cooled to 0° C., quenched slowly with EtOAc (15 mL), H2O (1.2 mL), NaOH (1.20 mL, 15% w/w in H2O) and H2O (3.60 mL). The resultant mixture was stirred for 1 h, diluted with EtOAc and filtered. The filter cake was taken up in 1N NaOH, extracted with diethyl ether and dried over MgSO4 to afford the title compound of step F (1.80 g, 7.70 mmol, 98%). 1H NMR (400 MHz, CD3OD) δ ppm 1.79 (t, J=10.8 Hz, 1H), 2.27-2.39 (m, 3H), 2.66 (tt, J=10.6, 2.1 Hz, 1H), 2.74 (ddd, J=10.8, 2.6, 2.4 Hz, 1H), 2.83 (dq, J=10.8, 2.2 Hz, 1H), 3.14-3.23 (m, 1H), 3.30 (dt, J=3.3, 1.6 Hz, 2H), 3.47-3.52 (m, 1H), 3.52-3.57 (m, 1H), 3.57-3.67 (m, 2H), 3.80 (dd, J=11.5, 3.5 Hz, 1H), 7.23-7.33 (m, 5H).

1. temperatureThe reaction was cooled to 0° C.
2. customquenched slowly with EtOAc (15 mL), H2O (1.2 mL), NaOH (1.20 mL, 15% w/w in H2O) and H2O (3.60 mL)
3. additiondiluted with EtOAc
4. filtrationfiltered
5. extractionextracted with diethyl ether
6. dry with materialdried over MgSO4