反应详情

Dimethylamine hydrochloride (1.406 g, 17.27 mmol) was suspended in dichloromethane (20 ml), and under nitrogen atmosphere at 0° C., trimethylaluminium (1.03 M n-hexane solution) (16.8 ml, 17.27 mmol) was gradually dropwise added. After stirring at room temperature for 30 minutes, a dichloromethane (20 ml) solution of ethyl 6-(3-chlorophenyl)-4-cyano-7-fluoro-5-methyl-1,3-benzoxazole-2-carboxylate (I-310) (2.065 g, 5.75 mmol) was dropwise added at 0° C. The solution was stirred for 21 hours with gradually heating up to room temperature, then at 0° C., aqueous 1 N hydrochloric acid solution (50 ml) was dropwise added, taking 15 minutes. After stirring at the same temperature for 30 minutes, the reaction liquid was extracted three times with dichloromethane. The organic layers were combined, washed with saturated brine, then dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, chloroform:acetone=99:1, v/v) to obtain the entitled compound (1.641 g, 80%) as a pale yellow solid.

1. stirringThe solution was stirred for 21 hours
2. temperaturewith gradually heating up to room temperature
3. waittaking 15 minutes
4. stirringAfter stirring at the same temperature for 30 minutes
5. customthe reaction liquid
6. extractionwas extracted three times with dichloromethane
7. washwashed with saturated brine
8. dry with materialdried over anhydrous sodium sulfate
9. customThe insoluble matter was separated by filtration
10. customthe solvent was evaporated away
11. customthe resulting residue was purified by middle-pressure liquid chromatography (eluent, chloroform