反应详情

温度

40 °C

The product of Example 449E (1.25 g, 2.0 mmol) in THF (12.5 mL) was reacted with aqueous LiOH solution [prepared from LiOH monohydrate (0.42 g, 10 mmol) and water (8.4 mL)] dropwise at room temperature. The mixture was stirred at 40° C. for 16 hours, and then concentrated. The aqueous mixture was diluted with 50 mL of water, washed with ethyl acetate (1×40 mL), and then carefully acidified to pH 5-6 with 1N HCl under stirring. After 30 minutes, the resulting precipitate was collected by filtration, washed with cold water, and dried at 40° C. for 3 days in vacuum to give the title compound as pale brown crystal (0.77 g, 87%). 1H-NMR (300 MHz, DMSO-d6) δ ppm: 1.34 (d, J=7. 0 Hz, 6H), 3.23 (septet, J=7.0 Hz, 1H), 5.67 (s, 2H), 7.15-7.30 (m, 2H), 6.81 (dd, J=9.2, 8.4 Hz, 1H), 6.91 (d, J=8.4 Hz, 1H), 7.02 (dd, J=8.4, 1.8 Hz, 1H), 7.11 (dd, J=11.4, 1.8 Hz, 1H), 7.64 (d, J=8.5 Hz, 1H), 7.76 (dd, J=8.4, 1.9 Hz, 1H), 7.86 (d, J=1.9 Hz, 1H), 8.57 (s, 1H), 8.85 (d, J=8.5 Hz, 1H), 10.12 (s, 1H). MS ESI+ m/z: 450 (M+H), ESI− m/z: 448 (M−H).

1. concentrationconcentrated
2. additionThe aqueous mixture was diluted with 50 mL of water
3. washwashed with ethyl acetate (1×40 mL)
4. stirringunder stirring
5. waitAfter 30 minutes
6. filtrationthe resulting precipitate was collected by filtration
7. washwashed with cold water
8. customdried at 40° C. for 3 days in vacuum