反应详情

A solution of methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoate (Intermediate 78, 2.73 g) in DCM (50 mL) was stirred at room temperature. DMF (5 drops) was added, followed by oxalyl chloride (2.0 g). After 30 minutes of stirring, the mixture was concentrated in vacuo and the residue was redissolved in DCM and evaporated to dryness. The residue was dissolved in DCM (50 mL) and aluminium chloride (3.38 g) was added. The resultant mixture was stirred at room temperature for 5 hours then diluted with more DCM and washed with ice/water. After separation, the aqueous phase was extracted with more DCM and the combined organic layers were washed with saturated aqueous sodium bicarbonate, 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 10-40% to give methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate (1.16 g) as a white crystalline solid.

1. concentrationthe mixture was concentrated in vacuo
2. dissolutionthe residue was redissolved in DCM
3. customevaporated to dryness
4. dissolutionThe residue was dissolved in DCM (50 mL)
5. additionaluminium chloride (3.38 g) was added
6. stirringThe resultant mixture was stirred at room temperature for 5 hours
7. additionthen diluted with more DCM
8. washwashed with ice/water
9. customAfter separation
10. extractionthe aqueous phase was extracted with more DCM
11. washthe combined organic layers were washed with saturated aqueous sodium bicarbonate
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationThe filtrate was concentrated in vacuo
15. customthe residue was purified by chromatography on silica
16. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 10-40%