反应详情

3,4-Dihydro-6-methyl-4-phenyl-2H-benzopyran-2-one (III, EXAMPLE 1, 100.0 g, 420.2 mmol) is added to toluene (500 mL). The mixture is degassed by purging alternately with vacuum and nitrogen and then cooled to -21°. Diisobutylaluminumhydride in toluene solution (DIBAL, 1.5M, 290 mL, 435 mmol) is then slowly added over 2 hr via add funnel while maintaining the reaction temperature at -20 to -25°. The reduction is usually done when the DIBAL add is completed. If the reaction is not done additional DIBAL can be added in increments. When the reaction is done (<1% lactone) ethyl acetate (45 mL) is added at -20° to -25° via add funnel. Very little exotherm is observed. Next, citric acid (23%, 500 mL) is added. The mixture is stirred at 45-50° for 1 hr (or stirred overnight at 20-25°), the phases are separated, the organic phase is washed with water (2×300 mL). The organic phase is concentrated to 250 mL under reduced pressure. Methanol (500 mL) is added, and the mixture is concentrated to 250 mL. The methanol addition and distillation is repeated to give the title compound in methanol solution. This solution is concentrated to a thick oil which crystallizes on standing to give the title compound (as a mixture of diastereomers), IR (neat) 3410, 3020, 2925, 1605, 1498, 1447, 1205 and 1010 cm-1 ; MS (m/z, EI)=240 (parent). Rather then isolating and characterizing the title compound, it is normally taken directly into the next step.

1. customThe mixture is degassed
2. customby purging alternately with vacuum and nitrogen
3. temperaturecooled to -21°
4. additionvia add funnel
5. temperaturewhile maintaining the reaction temperature at -20 to -25°
6. additionadd
7. additioncan be added in increments
8. additionis added at -20° to -25°
9. additionvia add funnel
10. stirring(or stirred overnight at 20-25°)
11. customthe phases are separated
12. washthe organic phase is washed with water (2×300 mL)
13. concentrationThe organic phase is concentrated to 250 mL under reduced pressure
14. additionMethanol (500 mL) is added
15. concentrationthe mixture is concentrated to 250 mL
16. additionThe methanol addition and distillation