3-Hydroxyanthranilic Acid → 2-(4-(((Benzyloxycarbonyl)(methyl)amino)methyl)phenyl)benzo[d]oxazole-4-carboxylic acid

Participants

Reaction Steps

To a suspension of 3-hydroxyanthranilic acid (0.300 g, 1.96 mmol) in toluene (10 mL) is added benzyl 4-(chlorocarbonyl)benzyl(methyl)carbamate (1.811 g, 5.7 mmol) followed by pyridine (0.545 g, 6.92 mmol) at room temperature. The resulting mixture is stirred at room temperature for 30 minutes then heated to 80° C. for 1 hr. After this time the reaction is cooled and poured into a mixture of ethyl acetate (50 mL) and 5% aqueous hydrochloric acid (50 mL). Subsequent separation of the layers, drying the organic over MgSO4 and filtration afford a solution. After removal of the solvent, the residue is dissolved in xylenes (20 mL) and the solution treated with p-TsOH (0.800 g, 4.20 mmol). The reaction mixture is then heated to reflux for 6 hrs. After this time the reaction is cooled and poured into water (50 mL), the organic layer is separated and then washed with water (3×50 mL). The organic is dried over MgSO4, filtered and concentrated to a solid. Flash column chromatography on silica gel using ethyl acetate and hexanes as the eluents gives a solid product, 2-(4-(((benzyloxycarbonyl)(methyl)amino)methyl)phenyl)benzo[d]oxazole-4-carboxylic acid. MS (ESI) m/e 417 [M+H]+.

Provenance & Evidence