3-amino-2-chloro-4-fluorophenol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (478 mg, 2.04 mmol, 1.1 eq) in DCM (9 mL) and DMF (3 drops) at 0° C. was added (COCl)2 (779 mg, 6.14 mmol, 3.3 eq) dropwise. The reaction mixture was stirred at room temperature for 1.5 h, then the solvent removed in vacuo. The residue obtained was dissolved in THF (7 mL) and added dropwise to a mixture of 3-amino-2-chloro-4-fluoro-phenol (intermediate X(f)) (300 mg, 1.86 mmol, 1.0 eq) and NaHCO3 (781 mg, 9.3 mmol, 5.0 eq) in THF (7 mL) at 0° C. After addition was completed, the reaction mixture was warmed to room temperature and stirred overnight. Water was added and the aqueous mixture was extracted with EtOAc. The organic extract was washed with 5% Na2CO3, water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4) to give the title as a yellow solid compound (180 mg, 26%). the solvent removed in vacuo The residue obtained After addition the reaction mixture was warmed to room temperature stirred overnight the aqueous mixture was extracted with EtOAc The organic extract was washed with 5% Na2CO3, water and brine dried (Na2SO4) filtered evaporated in vacuo purified by column chromatography (EtOAc:petroleum ether, 3:20 to 1:4)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-chloro-6-fluoro-3-methoxy-aniline (0.85 g, 4.84 mmol, 1.0 eq) in DCM (8 mL) at 0° C. was added BBr3 (6.06 g, 24.2 mmol, 5.0 eq). The mixture was stirred at room temperature under N2 overnight, then poured into ice-water. The pH of the solution was adjusted to pH 6 by addition of sat.NaHCO3. The dichloromethane was removed under reduced pressure and the aqueous residue was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na2SO4), filtered and evaporated in vacuo to give the title compound as a pale yellow solid (0.74 g, 95%). The pH of the solution was adjusted to pH 6 by addition The dichloromethane was removed under reduced pressure the aqueous residue was extracted with EtOAc The combined organic extracts were washed with brine dried (Na2SO4) filtered evaporated in vacuo