反应详情

温度

60 °C

A suspension of methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate (Intermediate 77, 1.32 g) in trichloroethylene (25 mL) was treated with DMF (1.5 mL), followed by dropwise addition of phosphorus oxychloride (0.998 g). The resultant mixture was heated at 60° C. for 2 hours. A further amount of phosphorus oxychloride (0.200 g) was added and the mixture was heated at 60° C. for 40 minutes. After cooling, the mixture was diluted with DCM and washed with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with DCM and the combined organic layers were washed with brine, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-25% to give methyl 7-tert-butylcarbonylamino-4-chloro-3-formyl-2H-chromene-8-carboxylate (1.175 g) as a yellow solid.

1. temperatureAfter cooling
2. washwashed with saturated aqueous sodium bicarbonate solution
3. extractionThe aqueous phase was extracted with DCM
4. washthe combined organic layers were washed with brine
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationThe filtrate was concentrated in vacuo
8. customthe residue was purified by chromatography on silica
9. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-25%