反应详情

A solution of crude 5-(3,5-Bis-trifluoromethyl-benzylamino)-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (200 mg, 0.42 mmol) and pyridine (0.85 ml, 10.5 mmol) in dichloromethane (2 ml) at room temperature was treated with acetic anhydride (0.79 ml, 8.4 mmol) via dropwise addition over 4 minutes. The mixture was stirred at room temperature for 20 hours. The mixture was cooled (0° C.) and treated with 1N NaOH and stirred for 30 minutes. The aqueous layer was extracted with dichloromethane. The combined organic phases were washed with 1N HCl, dried (Na2SO4) and concentrated to an oil. Purification by silica gel chromatography (eluent, 2:1 n-hexanes:ethyl acetate) provided 5-[Acetyl-(3,5-bis-trifluoromethyl-benzyl)-amino]-2,3,4,5-tetrahydro-benzo[b]azepine-1-carboxylic acid isopropyl ester (144 mg).

1. temperatureThe mixture was cooled (0° C.)
2. stirringstirred for 30 minutes
3. extractionThe aqueous layer was extracted with dichloromethane
4. washThe combined organic phases were washed with 1N HCl
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated to an oil
7. customPurification by silica gel chromatography (eluent, 2:1 n-hexanes:ethyl acetate)