反应详情

7-Hydroxy-1,2,4,5-tetrahydro-benzo[d]azepine-3-carboxylic acid tert-butyl ester (WO 02/40471) (5.27 g, 20.0 mmol), potassium carbonate (8.30 g, 60.0 mmol) and catalytic potassium iodide were suspended in butanone (100 ml). Methyl 4-(bromomethyl) benzoate (5.5 g, 24.0 mmol) dissolved in butanone (50 ml) was added dropwise after which the reaction mixture was stirred at reflux for 24 hours. The reaction mixture was cooled, the solids were filtered and then washed with acetone. The filtrate was concentrated in vacuo and the crude mixture was purified by column chromatography eluting with a mixture of ethyl acetate:hexane (1:4) to afford the title compound (D3). MS (ES+) m/e 344 [(M+H)—CO2tBu]+.

1. additionwas added dropwise after which the reaction mixture
2. temperatureat reflux for 24 hours
3. temperatureThe reaction mixture was cooled
4. filtrationthe solids were filtered
5. washwashed with acetone
6. concentrationThe filtrate was concentrated in vacuo
7. customthe crude mixture was purified by column chromatography
8. washeluting with a mixture of ethyl acetate:hexane (1:4)