反应详情

温度

0 °C

To a stirred mixture of piperidin-4-ylmethanol (5.0 g, 43.4 mmol), t-butyldimethylsilylchloride (7.2 g, 47.8 mmol), and triethylamine (7.3 mL, 52.1 mmol) in dichloromethane (50 mL) was added 4-dimethylaminopyridine (530 mg, 4.3 mmol) at 0° C. After being stirred at 0° C. for 2 h, 50 mL of water was added to the mixture. The mixture was extracted with dichloromethane (50 mL×3) and the extracts were combined, dried over sodium sulfate, and concentrated in vacuo to give 10.2 g of a crude oil. The residual oil was dissolved with 86 mL of ethanol, and potassium carbonate (7.2 g, 52.1 mmol) and paraformaldehyde (1.56 g, 52.1 mmol) were added to the solution. After being stirred at room temperature for 2 days, the mixture was filtered and the filtrate was concentrated in vacuo to give a yellow oil. The residual oil was dissolved with 45 mL of acetonitrile and magnesium chloride (414 mg, 4.3 mmol) was added to the solution. [methoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silane (11.3 g, 52.1 mmol, EXAMPLE 1, step 3) was added to the mixture at 0° C. After being stirred at 0° C. for 20 h, 100 mL of 2N hydrochloric acid was added to the mixture. The mixture was stirred for 30 min and washed with diethyl ether (100 mL×2). The water layer was neutralized with aq. ammonia and extracted with ethyl acetate (100 mL×2). The extracts were combined and dried over sodium sulfate and concentrated in vacuo to give a yellow oil. The residual oil was purified by silica gel column chromatography (dichloromethane/methanol/aq. ammonia 400:10:1) to give 6.8 g (41%) of the title compound as a colorless waxy solid.

1. extractionThe mixture was extracted with dichloromethane (50 mL×3)
2. dry with materialdried over sodium sulfate
3. concentrationconcentrated in vacuo
4. customto give 10.2 g of a crude oil
5. additionwere added to the solution
6. stirringAfter being stirred at room temperature for 2 days
7. filtrationthe mixture was filtered
8. concentrationthe filtrate was concentrated in vacuo
9. customto give a yellow oil
10. additionwas added to the solution
11. stirringAfter being stirred at 0° C. for 20 h
12. stirringThe mixture was stirred for 30 min
13. washwashed with diethyl ether (100 mL×2)
14. extractionextracted with ethyl acetate (100 mL×2)
15. dry with materialdried over sodium sulfate
16. concentrationconcentrated in vacuo
17. customto give a yellow oil
18. customThe residual oil was purified by silica gel column chromatography (dichloromethane/methanol/aq. ammonia 400:10:1)