N-methyl-2-pyrrolidone → Tert-butyl 2-oxo-8-(2-oxopyrrolidin-1-yl)-1,2,3,4-tetrahydroquinolin-3-ylcarbamate

Participants

Reaction Conditions

Reaction Steps

tert-Butyl 6-bromo-8-nitro-2-oxo-1,2,3,4-tetrahydroquinolin-3-ylcarbamate (200 g) was suspended in N-methylpyrrolidone (520 mL), and diisopropylethylamine (136.6 g) and 10% Pd—C (water content: 52.5%) (12.6 g) were added thereto. The reactor was washed with N-methylpyrrolidone (200 mL), and the wash liquid was combined with the mixture. The resultant mixture was purged with hydrogen three times, and the mixture was stirred vigorously for four hours while maintaining the internal temperature at 50-56° C. (formation of Compound A). The resultant mixture was cooled to 25° C., and the mixture was filtered through Celite. The filtered solid was washed with N-methylpyrrolidone (20 mL) three times. The filtrate was cooled to 8° C., and 4-chlorobutyryl chloride (80.3 g) was added dropwise thereto, followed by stirring at 14-17° C. for 20 minutes (formation of Compound B). To the resultant mixture was added dropwise 25% aqueous sodium hydroxide solution (265.2 g) over 12 minutes, and the mixture was stirred for 1.5 hours (formation of Compound C). Water (720 mL) was added to the resultant mixture, and stirring was continued for one hour. The formed precipitates were recovered through vacuum filtration, and the thus-recovered residue was washed three times with water (200 mL), whereby the title compound (154 g) (water content: 14%) was yielded as a powdery compound.

Provenance & Evidence