methyl 3-bromo-4-carbamoylbenzoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-(aminocarbonyl)benzoate (0.54 mmol) was dissolved in methanol (1 mL) and was treated with 1M aqueous sodium hydroxide (1 mL) at 45° C. for 3 h. The reaction mixture was cooled to room temperature and concentrated to afford an aqueous residue that was acidified with 1N aqueous hydrochloric acid to pH ˜3. The precipitate was collected by filtration, washed with water, and dried to afford 3-bromo-4-(aminocarbonyl)benzoic acid (69.4 mg, 0.28 mmol, 53% overall). 1H NMR (400 MHz, d6-DMSO): 13.47 (br s, 1H), 8.08 (dd, 1H), 8.00 (br s, 1H), 7.94 (dd, 1H), 7.73 (br s, 1H), 7.51 (d, 1H); MS (EI) for C8H6BrNO3: 242, 244(M−H). concentrated to afford an aqueous residue that The precipitate was collected by filtration washed with water dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-(aminocarbonyl)benzoate (0.54 mmol) was dissolved in methanol (1 mL) and was treated with 1M aqueous sodium hydroxide (1 mL) at 45° C. for 3 h. The reaction mixture was cooled to room temperature and concentrated to afford an aqueous residue that was acidified with 1N aqueous hydrochloric acid to pH ˜3. The precipitate was collected by filtration, washed with water, and dried to afford 3-bromo-4-(aminocarbonyl)benzoic acid (69.4 mg, 0.28 mmol, 53% overall). 1H NMR (400 MHz, d6-DMSO): 13.47 (br s, 1H), 8.08 (dd, 1H), 8.00 (br s, 1H), 7.94 (dd, 1H), 7.73 (br s, 1H), 7.51 (d, 1H); MS (EI) for C8H6BrNO3: 242, 244(M−H). concentrated to afford an aqueous residue that The precipitate was collected by filtration washed with water dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-cyanobenzoate (prepared as described in Wang, G. T. et al. Bioorg. Med. Chem. Lett. 2005, 15(1), 153(1) (130 mg, 0.54 mmol) was dissolved in DMSO (1.5 mL) and was cooled in a cold water bath. 30% aqueous hydrogen peroxide (0.1 mL) and potassium carbonate (23.9.0 mg, 0.17 mmol) were added and the mixture was stirred at room temperature for 18.5 h. The reaction mixture was partitioned between ethyl acetate and 10% aqueous lithium chloride. The aqueous portion was extracted with ethyl acetate. The combined organic portions were dried over sodium sulfate, filtered and concentrated to afford methyl 3-bromo-4-(aminocarbonyl)benzoate (quantitative yield) as a yellow oil. GCMS for C9H8BrNO3: 257, 259 (M+). was cooled in a cold water bath The reaction mixture was partitioned between ethyl acetate and 10% aqueous lithium chloride The aqueous portion was extracted with ethyl acetate The combined organic portions were dried over sodium sulfate filtered concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-(aminocarbonyl)benzoate (0.54 mmol) was dissolved in methanol (1 mL) and was treated with 1M aqueous sodium hydroxide (1 mL) at 45° C. for 3 h. The reaction mixture was cooled to room temperature and concentrated to afford an aqueous residue that was acidified with 1N aqueous hydrochloric acid to pH ˜3. The precipitate was collected by filtration, washed with water, and dried to afford 3-bromo-4-(aminocarbonyl)benzoic acid (69.4 mg, 0.28 mmol, 53% overall). 1H NMR (400 MHz, d6-DMSO): 13.47 (br s, 1H), 8.08 (dd, 1H), 8.00 (br s, 1H), 7.94 (dd, 1H), 7.73 (br s, 1H), 7.51 (d, 1H); MS (EI) for C8H6BrNO3: 242, 244(M−H). concentrated to afford an aqueous residue that The precipitate was collected by filtration washed with water dried

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methyl 3-bromo-4-cyanobenzoate (prepared as described in Wang, G. T. et al. Bioorg. Med. Chem. Lett. 2005, 15(1), 153(1) (130 mg, 0.54 mmol) was dissolved in DMSO (1.5 mL) and was cooled in a cold water bath. 30% aqueous hydrogen peroxide (0.1 mL) and potassium carbonate (23.9.0 mg, 0.17 mmol) were added and the mixture was stirred at room temperature for 18.5 h. The reaction mixture was partitioned between ethyl acetate and 10% aqueous lithium chloride. The aqueous portion was extracted with ethyl acetate. The combined organic portions were dried over sodium sulfate, filtered and concentrated to afford methyl 3-bromo-4-(aminocarbonyl)benzoate (quantitative yield) as a yellow oil. GCMS for C9H8BrNO3: 257, 259 (M+). was cooled in a cold water bath The reaction mixture was partitioned between ethyl acetate and 10% aqueous lithium chloride The aqueous portion was extracted with ethyl acetate The combined organic portions were dried over sodium sulfate filtered concentrated