methyl 4-amino-2-bromo-5-fluorobenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of the intermediate methyl 4-amino-2-bromo-5-fluorobenzoate (5.24 mmol, 1.3 g) in tetrahydrofuran (15 mL) was treated with a solution of lithium hydroxide (15.72 mmol, 0.66 g) in water (15 mL) and stirred at 60° C. for 4 hours. The reaction mixture was then cooled to room temperature, taken to ˜pH 5 with dilute hydrochloric acid and concentrated under vacuum. The residue was dissolved in tetrahydrofuran and purified by column chromatography (9:1 dichloromethane/methanol) to give the title compound (1.1 g). 1H NMR ((CD3)2SO, 400 MHz): δ6.11 (2H, s), 7.02 (1H, d), 7.52 (1H, d) The reaction mixture was then cooled to room temperature concentrated under vacuum The residue was dissolved in tetrahydrofuran purified by column chromatography (9:1 dichloromethane/methanol)

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

Procedure: A suspension of the methyl 4-(benzylamino)-2-bromo-5-fluorobenzoate (2.4 g, 7.10 mmol) in acetic acid was treated with 10% palladium on charcoal (250 mg) and stirred at room temperature under 2 bar hydrogen for 18 hours. The reaction mixture was then diluted with methanol, filtered through celite and evaporated to low volume. The residue was suspended in water (50 mL) and basified with 5% sodium carbonate solution then was extracted with ethyl acetate (2×). The combined organic phases were dried (sodium sulfate) and evaporated to a sandy solid. This crude solid was dissolved in the methanol and passed down an SCX cartridge. Evaporation of the methanol eluents gave the title compound (1.3 g). filtered through celite evaporated to low volume then was extracted with ethyl acetate (2×) The combined organic phases were dried (sodium sulfate) evaporated to a sandy solid This crude solid was dissolved in the methanol Evaporation of the methanol eluents