Water → 3-[4-({[(Tert-butoxy)carbonyl]amino}methyl)phenyl]benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of tert-butyl N-(4-bromobenzyl)carbamate (0.425 g), benzyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxa-borolane-2-yl)benzoate (0.553 g), sodium carbonate (0.315 g), water (1.3 mL) and N,N-dimethylformamide (6.5 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.086 g), and the resulting mixture was stirred at 80° C. for 70 minutes. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate (35 mL) and water (15 mL). The organic layer was washed successively with water/brine (2/1, 15 mL×2) and brine (15 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. To a solution of the residue (1.0 g) in ethanol (7.4 mL) was added 1 mol/L aqueous sodium hydroxide (2.23 mL), and the resulting mixture was stirred at 80° C. for 80 minutes. One mol/L aqueous sodium hydroxide (2.23 mL) was added and stirring was continued for additional 2 hours. The reaction mixture was cooled to room temperature. One mol/L hydrochloric acid (4.46 mL) was added and then the whole was partitioned between ethyl acetate (35 mL) and water (10 mL). The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=3/2-1/2) to give 4′-(tert-butoxycarbonylaminomethyl)biphenyl-3-carboxylic acid (0.388 g). To a solution of the carboxylic acid (0.330 g) in N,N-dimethylformamide (5.0 mL) were added successively dimethylamine hydrochloride (0.123 g), diphenylphosphoryl azide (0.435 mL) and triethylamine (0.422 mL), and the resulting mixture was stirred at room temperature for 67.5 hours. One mol/L hydrochloric acid (10 mL) was added and the whole was extracted with ethyl acetate (30 mL). The organic layer was washed successively with water (10 mL), saturated aqueous sodium hydrogen carbonate (10 mL) and brine (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/ethyl acetate=8/1) to give the title compound (0.246 g).

Provenance & Evidence