2-chloro-6-fluoro-3-methoxyaniline

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

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-benzoic acid (2.7 g, 13.2 mmol, 1.0 eq) in a mixture of DCM (20 mL) and DMF (3 drops) at 0° C. was added (COCl)2 (5.0 g, 39.6 mmol, 3.0 eq) dropwise. The reaction mixture was stirred at room temperature for 1 h, and then concentrated to dryness; the residue was dissolved in acetone (20 mL) and added dropwise to a solution of NaN3 (2.6 g, 39.6 mmol, 3.0 eq) in water (15 mL) at 0° C. The reaction was stirred 1 h at 0° C., water (50 mL) was added, then the reaction heated at 70° C. overnight. The acetone was removed by distillation and the aqueous residue extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo to give a residue, which was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:30) to give the title compound as a yellow oil (0.85 g, 37%). concentrated to dryness the residue was dissolved in acetone (20 mL) The reaction was stirred 1 h at 0° C. the reaction heated at 70° C. overnight The acetone was removed by distillation the aqueous residue extracted with EtOAc The combined organic extracts were washed with water and brine dried (Na2SO4) filtered evaporated in vacuo to give a residue, which was purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:30)