反应详情

To a solution of (2S,4R)-1-{1-benzyl-4-(t-butyl-dimethylsilyloxy) pyrrolidin-2-yl}-1-(1-methyl-4-pyrazolyl)methanol (70 g) in methanol (700 ml) was added ammonium formate (44 g) and 10% Pd-C (wet, 20 g). The mixture was refluxed for 40 minutes, then cooled. After filtration of Pd-C, the solvent was evaporated. To the residue was added chloroform (500 ml) and precipitated excess ammonium formate was filtered off with celite. The filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran-water (1:1, 1 l) and a solution of allyl chloroformate (22.3 ml) in tetrahydrofuran (60 ml) was added thereto, while adjusting pH to 8.5~10 with 4N-sodium hydroxide solution at 0°~5° C. The mixture was stirred for 30 minutes at the same temperature. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (×2). The combined organic layer was washed with water and brine, dried over magnesium sulfate and evaporated under reduced pressure to give 1-{(2S,4R)-1-allyloxy-carbonyl-4-(t-butyldimethylsilyloxy) pyrrolidin-2-yl}-1-(1-methylpyrazol-4-yl) methanol (66.2 g).

1. temperatureThe mixture was refluxed for 40 minutes
2. temperaturecooled
3. filtrationAfter filtration of Pd-C
4. customthe solvent was evaporated
5. additionTo the residue was added chloroform (500 ml)
6. customprecipitated excess ammonium formate
7. filtrationwas filtered off with celite
8. concentrationThe filtrate was concentrated under reduced pressure
9. dissolutionThe residue was dissolved in tetrahydrofuran-water (1:1, 1 l)
10. additiona solution of allyl chloroformate (22.3 ml) in tetrahydrofuran (60 ml) was added
11. customat 0°~5° C
12. customThe organic layer was separated
13. extractionthe aqueous layer was extracted with ethyl acetate (×2)
14. washThe combined organic layer was washed with water and brine
15. dry with materialdried over magnesium sulfate
16. customevaporated under reduced pressure