反应详情

Methyl (1aRS,7bSR)-5-(2,2-dimethylpropionylamino)-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (Intermediate 43, 0.310 g) was suspended in methanol (7.5 mL) and concentrated sulphuric acid (4 drops) was added. The reaction mixture was heated to reflux, under an atmosphere of nitrogen, for 36 hours. A further 2 drops of concentrated sulphuric acid was added and heating was continued for a further 24 hours. After cooling, the mixture was concentrated in vacuo and the residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate solution. The aqueous layer was extracted with ethyl acetate and the combined organic layers were 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 5-20% to give methyl (1aRS,7bSR)-5-amino-1,1a,2,7b-tetrahydrocyclopropa[c]chromene-4-carboxylate (0.120 g) as an off-white solid.

1. temperatureThe reaction mixture was heated
2. temperatureto reflux, under an atmosphere of nitrogen, for 36 hours
3. temperatureheating
4. temperatureAfter cooling
5. concentrationthe mixture was concentrated in vacuo
6. customthe residue was partitioned between ethyl acetate and saturated aqueous potassium carbonate solution
7. extractionThe aqueous layer was extracted with ethyl acetate
8. dry with materialthe combined organic layers were dried (Na2SO4)
9. filtrationfiltered
10. concentrationThe filtrate was concentrated in vacuo
11. customthe residue was purified by chromatography on silica
12. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 5-20%