反应详情

温度

90 °C

To a stirred solution of 1-(3,4-dichlorophenyl)-3-aza-bicyclo[3.1.0]hexane hydrochloride (30.0 g, 132 mmol) in 37% aqueous formaldehyde (25.8 mL) was added formic acid (32.4 mL). The resulting solution was stirred at 90° C. for 6 h. The reaction was then diluted with water (100 mL) and 2N aqueous sodium hydroxide added until the pH was greater than 9. The resulting mixture was extracted with CH2Cl2 (2×200 mL) and the combined organic extracts were washed with brine (200 mL), dried (MgSO4) and concentrated under vacuum to provide the title compound (25.0 g, 79% yield) as an orange oil: LC (ELS)/MS: >99%, m/z 242.1 [C12H13Cl2N+H]+; 1H NMR (300 MHz, CDCl3): δ 0.94 (dd, 1H, J=5.3 Hz, J=7.9 Hz), 1.73 (t, 1H, J=4.7 Hz), 1.80 (m, 1H), 2.55 (s, 3H), 2.78 (d, 2H, J=9.2 Hz), 3.35 (d, 1H, J=9.6 Hz), 3.54 (d, 1H, J=9.3 Hz), 6.99 (dd, 1H, J=2.1 Hz, J=8.3 Hz), 7.24 (d, 1H, J=2.1 Hz), 7.35 (d, 1H, J=8.3 Hz).

1. additionadded until the pH was greater than 9
2. extractionThe resulting mixture was extracted with CH2Cl2 (2×200 mL)
3. washthe combined organic extracts were washed with brine (200 mL)
4. dry with materialdried (MgSO4)
5. concentrationconcentrated under vacuum