Dimethylformamide → Benzyloxycarbonylaminoacetyl chloride

To a mixture of N-[(benzyloxy)carbonyl]glycine (0.78 g, 3.8 mmol), N,N-dimethylformamide (0.1 ml) and tetrahydrofuran (20 ml) was added dropwise oxalyl chloride (0.33 ml, 3.7 mmol) under ice-cooling. The mixture was stirred under ice-cooling for 1 hr. to give a crude product of N-[(benzyloxy)carbonyl]glycyl chloride. To a mixture of tert-butyl N-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]glycinate (0.40 g, 0.75 mmol), pyridine (0.3 ml, 3.7 mmol) and tetrahydrofuran (100 ml) was added dropwise the crude product. The obtained mixture was stirred for 1 hr. and 4-dimethylaminopyridine (0.01 g, 0.82 mmol) was added, and the mixture was stirred at room temperature for 2 days. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give tert-butyl N-[(benzyloxy)carbonyl]glycyl-N-[3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl]glycinate (0.47 g, yield 87%) as a white powder.

1. temperaturecooling
2. temperaturecooling for 1 hr

ORD record

ord-ff6efded905f4564b8793b80856b605d

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07547710B2