反应详情

A solution of potassium t-butoxide in t-butanol (1M, 15.7 mL, 15.7 mmol) was added to a solution of the product of Step A (4.80 g, 14.95 mmol) in anhydrous DMF (50 mL) at 0° C. followed by 1-bromo-3-methoxypropane (3.43 g, 22.4 mmol) and sodium iodide (0.2 g). The mixture was stirred for 5 h at ambient temperature, poured into ice water (300 mL) and extracted with ethyl acetate (2×200 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a viscous liquid which was dissolved in acetone (300 mL); p-toluenesulfonic acid (0.4 g) was added and this mixture was heated at reflux temperature for 4.5 h. A saturated aqueous solution of sodium bicarbonate (100 mL) was added to the reaction mixture and acetone was evaporated. The aqueous mixture was extracted with ethyl acetate (2×200 mL) and the combined extracts were dried (MgSO4), filtered and evaporated to give crude aldehyde which was dissolved in ethyl acetate (100 mL). DBN (0.2 g) was added and the mixture heated at reflux temperature for 2 h under nitrogen. The mixture was cooled, quenched with a 2N HCl (50 mL) and extracted with ethyl acetate (2×150 mL). The combined extracts were dried (MgSO4) and evaporated to a syrup which was purified by column chromatography (silica, 30% ethyl acetate/hexane) to give a white solid (2.68 g, 54%): mp 82°-83° C.

1. extractionextracted with ethyl acetate (2×200 mL)
2. dry with materialThe combined extracts were dried (MgSO4)
3. filtrationfiltered
4. customevaporated
5. customto give a viscous liquid which
6. temperaturethis mixture was heated
7. temperatureat reflux temperature for 4.5 h
8. customwas evaporated
9. extractionThe aqueous mixture was extracted with ethyl acetate (2×200 mL)
10. dry with materialthe combined extracts were dried (MgSO4)
11. filtrationfiltered
12. customevaporated
13. customto give crude aldehyde which
14. temperaturethe mixture heated
15. temperatureat reflux temperature for 2 h under nitrogen
16. temperatureThe mixture was cooled
17. customquenched with a 2N HCl (50 mL)
18. extractionextracted with ethyl acetate (2×150 mL)
19. dry with materialThe combined extracts were dried (MgSO4)
20. customevaporated to a syrup which
21. customwas purified by column chromatography (silica, 30% ethyl acetate/hexane)