反应详情

The title compound of Example 23 (10.0 g, 38.37 mmol) was heated to reflux in phosphorus oxychloride oxychloride (200 ml) and N,N-diethylaniline (3-4 drops) for 5 hours under nitrogen. The solution was then cooled to room temperature, concentrated to dryness, and the syrup was dissolved in cold (~-10° C.) methylene chloride (200 ml). The organic layer was treated with saturated aqueous sodium bicarbonate (100 ml) with vigorous stirring, and the temperature was kept below 5° C. as solid sodium bicarbonate was added portionwise to elevate the pH to between 5 and 7. The layers were separated and the aqueous phase was extracted with methylene chloride. The combined organic layers were filtered over phase-separator paper, concentrated and dried under vacuum to give the title compound (7.71 g, 72%) as a yellow-white solid sufficiently pure to employ in the next step. Recrystallisation of the solid from hexane/methylene chloride provided an analytical sample, m.p. 166°-169° C.; 1H-NMR (DMSO-d6) δ 1.09 (d, J=6.9 Hz, 6H, (CH3)2CH), 2.79 (m, J=6.9 Hz, 1H, (CH3)2CH), 11.61 (s, 1H).

1. concentrationconcentrated to dryness
2. dissolutionthe syrup was dissolved in cold (~-10° C.) methylene chloride (200 ml)
3. additionThe organic layer was treated with saturated aqueous sodium bicarbonate (100 ml) with vigorous stirring
4. customwas kept below 5° C. as solid sodium bicarbonate
5. additionwas added portionwise
6. customThe layers were separated
7. extractionthe aqueous phase was extracted with methylene chloride
8. filtrationThe combined organic layers were filtered over phase-separator paper
9. concentrationconcentrated
10. customdried under vacuum