Potassium Hydroxide → 5-Bromo-2-methoxy-4-methylaniline

Participants

Reaction Conditions

Reaction Steps

A 250 ml 3-neck RBF fitted with a magnetic stirring bar, a thermometer, a dropping funnel and a condenser was charged with 5-bromo-2-methoxy-4-methylbenzamide 12b (6 g, 24.6 mmol), anhydrous MeOH (40 mL) and 25% NaOMe solution in MeOH (21 mL, 98.4 mmol). This slurry was cooled to 5° C. and bromine (1.4 mL, 27.1 mmol) was added drop wise causing an exothermic reaction and the formation of a cloudy solution. The reaction mixture was stirred for 30 min at RT, and then heated to reflux for 1 hour. The solvent was removed under vacuum, the residue was re-dissolved in EtOH (50 mL) and KOH (5.5 g, 98.4 mmol) was added. The mixture was allowed to react under reflux for 16 hours in order to hydrolyze the intermediate methylcarbamate. Then the reaction mixture was diluted with H2O (300 mL) and the product was extracted into Et2O (3×100 mL). The combined organic layers were filtered through a pad of silica gel and evaporated to dryness to give 5-bromo-2-methoxy-4-methylaniline 12c (4.8 g, 90% yield) pure by 1H NMR as a light brown solid.

Provenance & Evidence