反应详情

To a solution of 2-(5-(3-chloro-2-fluorobenzyl)-2-fluoro-4-methoxybenzoyl)-3-((S)-1-hydroxymethyl-2-methylpropylamino)acrylic acid ethyl ester prepared in Step IX or Step III in N,N-dimethylformamide was added anhydrous potassium carbonate (4.86 g) with stirring at room temperature. After stirring at 95-105° C. for 6 hr, N,N-dimethylformamide (10 ml) and water (50 ml) were successively added dropwise at 65-75° C. to allow crystallization. After stirring for 1 hr, the mixture was cooled to room temperature and further stirred for 1 hr. Water (20 ml) was further added and, after stirring for 1 hr, the mixture was filtered, and the residue was washed successively with 50% aqueous N,N-dimethylformamide solution (20 ml) and water (20 ml), and vacuum dried to give 6-(3-chloro-2-fluorobenzyl)-1-((S)-1-hydroxymethyl-2-methylpropyl)-7-methoxy-4-oxo-1,4-dihydroquinoline)-3-carboxylic acid ethyl ester (13.5 g)).

1. stirringAfter stirring at 95-105° C. for 6 hr
2. customcrystallization
3. stirringAfter stirring for 1 hr
4. temperaturethe mixture was cooled to room temperature
5. stirringfurther stirred for 1 hr
6. additionWater (20 ml) was further added
7. stirringafter stirring for 1 hr
8. filtrationthe mixture was filtered
9. washthe residue was washed successively with 50% aqueous N,N-dimethylformamide solution (20 ml) and water (20 ml), and vacuum
10. customdried