反应详情

n-Butyl lithium (2.5M solution in hexane, 53.1 ml, 132.7 mmol) was added slowly to a stirred and cooled (−30° C.) solution of pyrrolidine (11.0 ml, 132.7 mmol) in dry tetrahydrofuran (100 ml). The solution was stirred at −25° C. for 1 hour. The above freshly prepared solution of lithium pyrrolidine was transferred slowly by cannula to a stirred and cooled (−35° C.) solution of the acetals III (18.7 g, 44.2 mmol) in dry tetrahydrofuran (200 ml). The mixture was stirred for 1 hour at −35° C. Iodomethane (6.9 ml, 110.6 mmol) was added slowly and the mixture was stirred for another 1 hour. Water (20 ml) was added to quench the reaction. After the cold bath was removed, saturated aqueous ammonium chloride solution (300 ml) was added and the mixture was stirred for 30 min. The mixture was extracted with toluene (3×250 ml). The combined organic extracts were washed with water (2×250 ml) and dried (Na2SO4). Evaporation of solvent gave crude acetal dimethylbutanoates IV (18.5 g, yield 96%) as a light brown syrup (HPLC purity >93%). This was used without further purification in the next step.

1. stirringThe solution was stirred at −25° C. for 1 hour
2. stirringa stirred
3. stirringThe mixture was stirred for 1 hour at −35° C
4. stirringthe mixture was stirred for another 1 hour
5. customto quench
6. customthe reaction
7. customAfter the cold bath was removed
8. additionsaturated aqueous ammonium chloride solution (300 ml) was added
9. stirringthe mixture was stirred for 30 min
10. extractionThe mixture was extracted with toluene (3×250 ml)
11. washThe combined organic extracts were washed with water (2×250 ml)
12. dry with materialdried (Na2SO4)
13. customEvaporation of solvent