反应详情

To a solution of benzyl 3-(2-amino-1-(2-fluorophenyl)ethyl)-1H-indol-6-ylcarbamate (0.586 g, 1.452 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.576 mL, 2.90 mmol) in 1,4-dioxane (15 mL) at room temperature was added hydrogen chloride in 1,4-dioxane (0.436 mL, 1.743 mmol). The mixture was stirred room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (30 mL), basified with NaHCO3 solution to pH 10, and extracted with ethyl acetate (3×30 mL). The combined extract was washed with brine (30 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added toluene (15 mL) and 10% Pd/C (0.2 g), and the mixture was heated at 110° C. under an ambient atmosphere for 3.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (100 ml), washed with brine (25 ml), and dried over anhydrous MgSO4. The desired product (0.238 g, 0.492 mmol, 33.9% yield) was isolated as a beige solid by ISCO (40 g silica gel, solid loading, 20-40% ethyl acetate/hexane).

1. customThe volatiles were removed under vacuum
2. additionThe residue was diluted with water (30 mL)
3. extractionextracted with ethyl acetate (3×30 mL)
4. extractionThe combined extract
5. washwas washed with brine (30 ml)
6. dry with materialdried over anhydrous MgSO4
7. concentrationconcentrated to dryness under vacuum
8. additionTo the residue were added toluene (15 mL) and 10% Pd/C (0.2 g)
9. temperaturethe mixture was heated at 110° C. under an ambient atmosphere for 3.5 hr
10. customThe solid phase was removed by suction filtration
11. additionThe filtrate was diluted with ethyl acetate (100 ml)
12. washwashed with brine (25 ml)
13. dry with materialdried over anhydrous MgSO4