反应详情

To a solution of 4-bromo-1-methylpyrazole (170.7 g) in diethyl ether (2 l) was added dropwise n-butyllithium (1.6N) in hexane (713 ml) keeping the temperature below -60° C. After stirring for 45 minutes, a solution of (2S,4R)-1-benzyl-4-(t-butyldimethylsilyloxy)-2-formylpyrrolidine (260 g) in diethyl ether (200 ml) was added dropwise. After stirring for 30 minutes, the mixture was warmed to 0°~5° C. over 2.5 hours and stirred for 45 minutes. The reaction mixture was quenched with ice water (1 l) 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 (3.5 kg, eluting with n-hexane:AcOEt=3:2 to 1:1 to 0:1) to give (2S,4R)-1-{1-benzyl-4-(t-butyldimethyl-silyloxy) pyrrolidin-2-yl}-1-(1-methyl-4-pyrazolyl)methanol (211.2 g) as a 1:1 mixture of diastereomers.

1. customthe temperature below -60° C
2. stirringAfter stirring for 30 minutes
3. temperaturethe mixture was warmed to 0°~5° C. over 2.5 hours
4. stirringstirred for 45 minutes
5. customThe reaction mixture was quenched with ice water (1 l)
6. customthe organic layer was separated
7. extractionThe aqueous layer was extracted with ethyl acetate (×2)
8. washthe combined organic layer was washed with water and brine
9. dry with materialdried over magnesium sulfate
10. customevaporated under reduced pressure
11. customchromatographed on silica gel (3.5 kg, eluting with n-hexane:AcOEt=3:2 to 1:1 to 0:1)