反应详情

Benzyl 4-[5-(diethoxymethyl)-1-methyl-1H-pyrazol-3-yl]phenylcarbamate (Intermediate 11, 8.29 g, 20.2 mmol), was dissolved in THF (150 ml) and cooled to −70° C. nBuLi (15 ml of a 1.6 M solution in hexanes, 24 mmol) was added dropwise over 10 min. After 25 min at −70° C., (2R)-oxiran-2-ylmethyl butyrate (3.7 ml, 26.2 mmol) was added and the solution was allowed to warm slowly to room temperature over 16 hours. The mixture was poured into 0.25M HCl and extracted with ethyl acetate, the organic layer was washed with saturated NaCl, dried over sodium sulfate and evaporated to give the crude product which was partially hydrolysed to the aldehyde. The crude product was dissolved in 1:1 THF:methanol (12 ml), trimethyl orthoformate (2.6 ml, 24 mmol) and camphorsulfonic acid (100 mg, 0.4 mmol) were added and the solution was warmed at 50° C. for 1 hour. Triethylamine (0.5 ml) was added and the solution was evaporated and purified by chromatography on silica gel, eluting with 60–100% ethyl acetate/hexane, to give the title compound as a white solid (3.47 g).

1. additionwas added dropwise over 10 min
2. extractionextracted with ethyl acetate
3. washthe organic layer was washed with saturated NaCl
4. dry with materialdried over sodium sulfate
5. customevaporated
6. customto give the crude product which
7. temperaturethe solution was warmed at 50° C. for 1 hour
8. customthe solution was evaporated
9. custompurified by chromatography on silica gel
10. washeluting with 60–100% ethyl acetate/hexane