反应详情

Dissolve 3-(2,6-Dichloro-4-methoxy-benzyl)-1-(1,4-dioxa-spiro[4.5]dec-8-yl)-pyrrolidin-2-one (6.5 g, 15.7 mmol) in acetone (100 mL), add p-toluenesulfonic acid hydrate (3 g, 15.7 mmol) and stir for 24 hr at room temp. Add 5N HCl (10 mL) and heat to 45° C. for 1 hr. Reaction progress can be monitored by TLC. Concentrate the reaction mixture, dilute with saturated aqueous sodium hydrogen carbonate (500 mL) and extract with ethyl acetate (3×150 mL). Wash the combined extracts with water (100 mL) and brine (100 mL), dry over anhydrous sodium sulfate, filtered, and concentrate to about 50 mL volume, dilute with hexanes (50 mL) and filter to give 5.5 g, 95%, as a white solid. 1H NMR (CDCl3) δ 6.78 (s, 2H), 4.44-4.52 (m, 1H), 3.78 (s, 3H), 3.37-3.47 (m, 1H), 3.29-3.36 (m, 1H), 3.15-3.23 (m, 2H), 2.39-2.62 (m, 4H), 1.80-2.11 (m, 6H). LCMS m+1 370.

1. temperatureheat to 45° C. for 1 hr
2. customReaction progress
3. concentrationConcentrate the reaction mixture
4. additiondilute with saturated aqueous sodium hydrogen carbonate (500 mL)
5. extractionextract with ethyl acetate (3×150 mL)
6. washWash the combined extracts with water (100 mL) and brine (100 mL)
7. dry with materialdry over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrate to about 50 mL volume
10. additiondilute with hexanes (50 mL)
11. filtrationfilter
12. customto give 5.5 g, 95%