Hydrochloric Acid → [3-(Methylamino)phenyl]boronic acid

Participants

Reaction Conditions

Reaction Steps

37.6 g (202 mmol, 1 eq) of (3-bromophenyl)methylamine (obtained as in 1c) are dissolved in 300 mL of tetrahydrofuran. The reaction mixture is cooled to −70° C. and 166 mL (242 mmol, 1.2 eq) of 1.5 M methyllithium are then added slowly, while keeping the temperature at −70° C. The reaction mixture is stirred for 1 hour at −70° C. 306 mL (444 mmol, 2.2 eq) of 1.46 M tert-butyllithium are added, while keeping the temperature at −70° C. The reaction mixture is stirred for 45 minutes at −70° C. 103.5 ml (808 mmol, 4 eq) of trimethyl borate are added at −65° C. and the reaction mixture is then warmed to room temperature. The reaction is stopped by adding 1 L of 1N hydrochloric acid. The pH is adjusted to pH 5 and the reaction medium is then extracted with n-butanol. The organic phases are combined and dried over sodium sulfate. The solvents are evaporated off and the residue is then chromatographed on silica gel (70/30 heptane/ethyl acetate). 11.3 g of N-methyl-3-aminophenylboronic acid are obtained. Yield=40%.

Provenance & Evidence