Diisopropylamine → 4-Bromo-2-(carboxymethyl)benzoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (13.26 mL, 93 mmol, 4.0 equiv.) in THF (50 mL) was slowly added n-BuLi (37.2 mL, 93 mmol, 4.0 equiv.) at −78° C. The mixture was allowed to warm to 0° C. and stirred at that temperature for 5 min. The reaction was cooled back to −78° C. and to this mixture was slowly added 4-bromo-2-methylbenzoic acid (5.0 g, 23.25 mmol) and dimethyl carbonate (3.91 mL, 46.5 mmol, 2.0 equiv.) in THF (50 mL) and the mixture was stirred at −78° C. for 5 min. The dry ice bath was removed and the reaction was allowed to stir at room temperature for 4 h. Upon completion of the reaction, the mixture was quenched by the addition of 75 mL water and allowed to stir overnight. The aqueous layer was separated from the organic layer. The aqueous layer was acidified with conc. HCl until pH 2, extracted with EtOAc (2×50 mL), dried over Na2SO4, filtered and evaporated to dryness to yield a white solid. The solid was recrystallized from hot EtOAc/hexanes to yield 5.65 g of 4-bromo-2-(carboxymethyl)benzoic acid as a white solid.

Provenance & Evidence