反应详情

温度

120 °C

To a solution of dimethyl methylphosphonate (8.9 g, 71.1 mmol) in dry THF (55 mL) under N2 was added, dropwise over 1 h at −70° C., n-butyllithium in hexane (1.6M, 49.2 mL). The mixture was stirred for 30 minutes at −70° C., whereafter a solution of 6-chloro-8-difluoromethoxychroman-4-one (6.8 g, 27.35 mmol, from step (v) above) in dry THF (15 mL) was added, dropwise over 30 minutes at −70° C. The reaction mixture was stirred for 2 h at −70° C., whereafter NH4Cl (aq., sat., 110 mL) was added, and then water (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was dissolved in DMF (85 mL). To the solution was added anhydrous potassium carbonate (27.4 g, 201.0 mmol) and water (3.6 ml). The mixture was warmed for 2 h at 120° C. (oil-bath). After the mixture had reached room temperature water (80 mL) was added. The mixture was extracted with EtOAc. The combined organic layers were washed with citric acid (aq., 10%) and with brine, dried (Na2SO4) and evaporated. The crude product was chromatographed on silica gel, eluting with heptane:methylene chloride (8:2), to afford 3.2 g (47%) of the sub-title compound.

1. additionwas added, dropwise over 30 minutes at −70° C
2. additionwas added
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with EtOAc
5. washThe combined organic layers were washed with brine
6. dry with materialdried (Na2SO4)
7. concentrationconcentrated
8. dissolutionThe residue was dissolved in DMF (85 mL)
9. customhad reached room temperature
10. additionwas added
11. extractionThe mixture was extracted with EtOAc
12. washThe combined organic layers were washed with citric acid (aq., 10%) and with brine
13. dry with materialdried (Na2SO4)
14. customevaporated
15. customThe crude product was chromatographed on silica gel
16. washeluting with heptane:methylene chloride (8:2)