Methyl 4-anilinobenzoate → Methyl Carbazole-3-Carboxylate

Participants

Reaction Steps

A mixture of dicylcohexylphosphino-2′,3′-dimethoxy biphenyl (17 mg, 0.04 mmol), palladium(II) acetate (5 mg, 0.02 mmol) in toluene (20 mL) was degassed with argon gas for 15 min. To the resulting mixture was added aniline (136 mg, 1.4 mmol), K3PO4 (636 mg, 3.0 mmol), and 4-bromobenzoic acid methyl ester (300 mg, 1.4 mmol) and stirring was continued at reflux temperature overnight. After completion of the reaction, the reaction mixture was filtered through celite and the filtrate collected was concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 15% ethyl acetate in hexane as eluent) to afford 200 mg (63.4% Yield) of 4-phenylamino-benzoic acid methyl ester. A stirred solution of 4-phenylamino-benzoic acid methyl ester (98 mg, 0.43 mmol), Palladium acetate (193 mg, 0.86 mmol) in acetic acid (2 mL) was heated at 110° C. for 15 hr. After completion of the reaction, the reaction mixture was diluted with water, extracted with ethyl acetate and washed with sodium bicarbonate solution. The organic layer collected was dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (using 60-120 silica gel and 10% ethyl acetate in hexane as eluent) to afford 120 mg (60.3% Yield) of 9H-carbazole-3-carboxylic acid methyl ester. LiOH.H2O (680 mg, 16.2 mmol) was added to a stirred solution of 9H-carbazole-3-carboxylic acid methyl ester (120 mg, 0.53 mmol) in the mixture of methanol (1 mL), THF (3 mL) and H2O (1 mL). The reaction mixture was stirred at 60° C. for 3 hrs. The reaction mixture was concentrated. The residue was diluted with water, acidified with aqueous 10% aqueous HCl solution, filtered the solid to afford 104 mg (92.85% Yields) of 9H-carbazole-3-carboxylic acid.

Provenance & Evidence