反应详情

Potassium tert-butoxide (1M, 4.54 ml) is added to 1,2,3,4-tetrahydro-3,3-dimethylquinoxalin-2-one (IV, EXAMPLE 2, 0.762 g) in THF (4 ml) at ice/saline temperature. The reaction is stirred for 40 min, at which time diethyl chlorophosphate (0.656 ml) is added. After stirring at ice-saline temperature for 2 hr, ethyl isocyanoacetate (0.562 g) is added, followed by potassium t-butoxide (1M, 4.97 ml). The reaction is stirred for 3.5 hr, allowing it to slowly warm to 20°-25°. The reaction is then quenched with several drops of acetic acid and then partitioned between ethyl acetate, aqueous sodium bicarbonate and saline. The phases are separated and the organic phase is dried over magnesium sulfate, concentrated, and the resulting crude product chromatographed on silica gel (200 ml) eluting with methanol/dichloromethane (2/98). The appropriate fractions are pooled and concentrated to give the title compound, mp 145°-149°; NMR (CDCl3) 1.44, 1.74, 3.79, 4.40, 6.77, 6.82, 7.10, and 7.39 δ.

1. additionis added
2. stirringThe reaction is stirred for 3.5 hr
3. temperatureto slowly warm to 20°-25°
4. customThe reaction is then quenched with several drops of acetic acid
5. custompartitioned between ethyl acetate, aqueous sodium bicarbonate and saline
6. customThe phases are separated
7. dry with materialthe organic phase is dried over magnesium sulfate
8. concentrationconcentrated
9. customthe resulting crude product chromatographed on silica gel (200 ml)
10. washeluting with methanol/dichloromethane (2/98)
11. concentrationconcentrated