反应详情

To a solution of 1-methylpyrazole (30.5 g) in tetrahydrofuran (460 ml) was added dropwise n-butyllithium (1.6N) in hexane (250 ml) keeping the temperature below -60° C. The mixture was warmed to 0°-5° C. over 30 minutes, and stirred for 30 minutes, then cooled to -70°~60° C. To the mixture was added a solution of (2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy)-2-formylpyrrolidine (91.4 g) in tetrahydrofuran (90 ml) keeping the temperature below -60° C. The reaction mixture was warmed to 0°-5° C. over 40 minutes, and stirred for 2 hours. The mixture was quenched with ice water (300 ml) and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (×2), and the combined organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure. The residue was column chromatographed on silica gel (3 kg, eluting with ethyl acetate-n-hexane (1:1 to 5:1)) to give 1-{(2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy)-pyrrolidin-2-yl }-1-(1-methylpyrazol-5-yl)methanol (101 g) (as a 2:1 mixture of diastereomer).

1. customthe temperature below -60° C
2. temperatureThe mixture was warmed to 0°-5° C. over 30 minutes
3. temperaturecooled to -70°~60° C
4. customthe temperature below -60° C
5. temperatureThe reaction mixture was warmed to 0°-5° C. over 40 minutes
6. stirringstirred for 2 hours
7. customThe mixture was quenched with ice water (300 ml)
8. customthe organic layer was separated
9. extractionThe aqueous layer was extracted with ethyl acetate (×2)
10. washthe combined organic layer was washed with water and brine
11. dry with materialdried over magnesium sulfate
12. customevaporated under reduced pressure
13. customchromatographed on silica gel (3 kg, eluting with ethyl acetate-n-hexane (1:1 to 5:1))