ethyl 4-amino-2,5-difluorobenzoate

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

Procedure: A solution of 4-amino-2,5-difluorobenzoic acid (intermediate 137; 2.7 g; 0.015 mol) in hydrogen chloride 1.25 mL in ethanol (91 mL, 0.113 mol) was stirred for 24 hours at 60° C. The solvent was removed under reduced pressure and the crude obtained was treated with water and solid bicarbonate to obtain a basic pH, after few minutes stirring an extraction with ethyl acetate was done. The organic layer was washed with brine, dried and the solvent was removed under reduced pressure to give the title compound as a white solid (92%), which was used in the next step without further purification. The solvent was removed under reduced pressure the crude obtained to obtain a basic pH an extraction with ethyl acetate The organic layer was washed with brine dried the solvent was removed under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-amino-2,5-difluorobenzonitrile (6.21 g, 38.28 mmol) in dioxane (32.5 mL) was added sulphuric acid 73% (52.2 mL) and the resulting mixture was stirred at 80° C. for 4 days. The crude reaction was added into water (250 mL) and basified with sodium hydroxide 32% (220 mL) until basic pH. The mixture was washed with methylene chloride and the aqueous phase was neutralized and extracted with ethyl acetate. The resulting organic phase was washed with brine, dried and filtered. The solvent was removed under reduced pressure to give the title compound as a white solid (42%), which was used in the next step without further purification. The crude reaction The mixture was washed with methylene chloride extracted with ethyl acetate The resulting organic phase was washed with brine dried filtered The solvent was removed under reduced pressure

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

Procedure: A solution of 4-amino-2,5-difluorobenzoic acid (intermediate 137; 2.7 g; 0.015 mol) in hydrogen chloride 1.25 mL in ethanol (91 mL, 0.113 mol) was stirred for 24 hours at 60° C. The solvent was removed under reduced pressure and the crude obtained was treated with water and solid bicarbonate to obtain a basic pH, after few minutes stirring an extraction with ethyl acetate was done. The organic layer was washed with brine, dried and the solvent was removed under reduced pressure to give the title compound as a white solid (92%), which was used in the next step without further purification. The solvent was removed under reduced pressure the crude obtained to obtain a basic pH an extraction with ethyl acetate The organic layer was washed with brine dried the solvent was removed under reduced pressure

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-amino-2,5-difluorobenzonitrile (6.21 g, 38.28 mmol) in dioxane (32.5 mL) was added sulphuric acid 73% (52.2 mL) and the resulting mixture was stirred at 80° C. for 4 days. The crude reaction was added into water (250 mL) and basified with sodium hydroxide 32% (220 mL) until basic pH. The mixture was washed with methylene chloride and the aqueous phase was neutralized and extracted with ethyl acetate. The resulting organic phase was washed with brine, dried and filtered. The solvent was removed under reduced pressure to give the title compound as a white solid (42%), which was used in the next step without further purification. The crude reaction The mixture was washed with methylene chloride extracted with ethyl acetate The resulting organic phase was washed with brine dried filtered The solvent was removed under reduced pressure