3-amino-2-fluoro-4-methylphenol

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

Procedure: To a mixture of 2 fluoro-5-(3-fluorophenyl) benzoic acid (intermediate III(a)) (730 mg, 3.1 mmol, 1.1 eq) and (COCl)2 (1.1 g, 8.49 mmol, 3 eq) in DCM (20 mL) was added DMF (5 drops). The reaction mixture was stirred at 0° C. for 1h and then concentrated in vacuo. The residue obtained was dissolved in THF (5 mL) and added dropwise to a solution of 3-amino-2-fluoro-4-methyl-phenol (400 mg, 2.83 mmol, 1 eq) 25 and NaHCO3 (951 mg, 11.3 mmol, 4 eq) in THF (15 mL) at 0° C. After the addition, the reaction mixture was stirred at room temperature for 3h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4) to give the title compound as a yellow solid (600 mg, 60%). concentrated in vacuo The residue obtained After the addition extracted with EtOAc The organic extract was washed with water and brine dried (Na2SO4) filtered evaporated in vacuo The residue was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:4)