反应详情

温度

0 °C

To a suspension of Intermediate 62A (0.250 g, 1.29 mmol) in MeOH (2 mL) at room temperature was added anhydrous hydrazine (0.048 mL, 1.55 mmol), and the mixture was heated to reflux for 1 hour. The suspension was cooled and filtered, washing the solid with MeOH. The solid was dried in vacuo and used immediately. The acyl hydrazide was suspended in 2N HCl (5 mL) and cooled to 0° C., whereupon sodium nitrite (0.533 g, 7.72 mmol) was added slowly in portions with vigorous stirring. The resulting solution stirred for 1 hour at 0° C. The reaction was then quenched by carefully adding solid sodium bicarbonate to pH 6, whereupon a precipitate formed. The solid was filtered, washed with cold water, and dried in vacuo overnight to provide Intermediate 62B (0.182 g, 68% yield) as a white solid. HPLC: Rt=2.345 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.82 (1H, s), 8.58 (1H, s), 8.52 (1H, d, J=5.29 Hz), 7.51 (1H, dd, J=5.16, 1.64 Hz), 2.11 (3H, s).

1. temperaturethe mixture was heated
2. temperatureto reflux for 1 hour
3. temperatureThe suspension was cooled
4. filtrationfiltered
5. washwashing the solid with MeOH
6. customThe solid was dried in vacuo
7. additionwas added slowly in portions with vigorous stirring
8. customThe reaction was then quenched
9. additionby carefully adding solid sodium bicarbonate to pH 6
10. customwhereupon a precipitate formed
11. filtrationThe solid was filtered
12. washwashed with cold water
13. customdried in vacuo overnight