反应详情

The 5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-benzaldehyde (10.34 g) described in example 1.4 was dissolved in ethanol (160 ml). 4-Aminobenzonitrile (4.87 g) was added and stirred at room temperature. After 1 hour, 5.68 ml of morpholinoethyl isonitrile was added. The solution obtained was cooled to 0° C., then treated dropwise with 15.53 ml of boron trifluoride etherate in a manner such that the temperature did not exceed 5° C. The reaction mixture was stirred at 0° C. for 15 min and at room temperature for 1.5 h. Water (20 ml) was added and stirred overnight at room temperature. The crude product was isolated by extraction and purified by chromatography on silica gel and yielded 11.13 g of (RS)-(4-cyano-phenylamino)-[5-ethoxy-2-fluoro-4-(2-hydroxy-ethoxy)-phenyl]-acetic acid ethyl ester as a yellowish solid. MS: 425 ([M+Na]+).

1. customThe solution obtained
2. temperaturewas cooled to 0° C.
3. customdid not exceed 5° C
4. stirringThe reaction mixture was stirred at 0° C. for 15 min and at room temperature for 1.5 h
5. stirringstirred overnight at room temperature
6. customThe crude product was isolated by extraction
7. custompurified by chromatography on silica gel