反应详情

温度

-20 °C

A 4-L reactor equipped with a mechanical stirrer, under nitrogen, was charged with (3aR,4R,5R,6aS)-4-formyl-2-oxohexahydro-2H-cyclopenta[b]furan-5-yl benzoate (Cayman Chemical Catalog #70030, 99.2 g, 0.362 mol) in dichloromethane and lithium chloride (16.7 g, 0.398 mol) dissolved in tetrahydrofuran. Dimethyl 2-oxo-3-phenoxypropylphosphonate (102.7 g, 0.398 mol) is added neat and rinsed with dichloromethane (50 mL). Some lithium chloride precipitated from solution when the THF and DCM solutions were mixed. The mixture was stirred under nitrogen and cooled to −20° C. After adding the phosphonate and subsequent stirring and cooling, the precipitated lithium chloride dissolved. After stirring for 2.5 hours, triethylamine (40.2 g, 0.398 mol) was added neat via addition funnel and the temperature was held at −5° C. and stirred at this temperature for 19 hours. The temperature was adjusted to 0° C. and treated with 5% aqueous citric acid and the layers were separated. The organic layer was dried over magnesium sulfate and filtered. The crude product was purified on silica gel, eluted with ethyl acetate-hexanes (1:1). The desired product precipitated from the product-rich fractions as a white fluffy solid. After further purification of mixed fractions, all the purified product crystallized from MTBE to afford the title intermediate (74.4 g, 50.6%) as a white solid.

1. customA 4-L reactor equipped with a mechanical stirrer, under nitrogen
2. washrinsed with dichloromethane (50 mL)
3. customSome lithium chloride precipitated from solution when the THF and DCM solutions
4. additionwere mixed
5. additionAfter adding the phosphonate
6. stirringsubsequent stirring
7. temperaturecooling
8. dissolutionthe precipitated lithium chloride dissolved
9. stirringAfter stirring for 2.5 hours
10. customwas held at −5° C.
11. stirringstirred at this temperature for 19 hours
12. customwas adjusted to 0° C.
13. customthe layers were separated
14. dry with materialThe organic layer was dried over magnesium sulfate
15. filtrationfiltered
16. customThe crude product was purified on silica gel
17. washeluted with ethyl acetate-hexanes (1:1)
18. customThe desired product precipitated from the product-rich fractions as a white fluffy solid
19. customAfter further purification of mixed fractions
20. customall the purified product crystallized from MTBE