ethyl 2-(2,4-difluoroanilino)-2-oxoacetate

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

Procedure: To a stirred solution of triphenylphosphine (629 mg, 2.40 mmol) and Intermediate 11A (458 mg, 2.00 mmol) in ClCH2CH2Cl (1 mL) was added dimethyl but-2-ynedioate (0.26 mL, 2.1 mmol) drop wise at rt. The reaction mixture was stirred at 80° C. in a capped vial for 18 h. The reaction mixture was allowed to cool to rt, loaded on to a 40 g silica gel column and purified with 0-100% EtOAc/Hex to give Intermediate 11B (560 mg, 1.58 mmol, 79.0% yield) as a slightly tan viscous oil. HPLC/MS (Method L) RT=1.77 min, [M+H]+ 356.0. to cool to rt purified with 0-100% EtOAc/Hex

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

Procedure: To a solution of 2,4-difluoroaniline (10 g, 77 mmol) and triethylamine (12.95 mL, 93.00 mmol) in THF (50 mL) was added ethyl 2-chloro-2-oxoacetate (9.05 mL, 81.0 mmol) drop wise at 0° C. A white solid precipitated instantly. The reaction mixture was stirred at rt for 1 h. The solvent was evaporated, and Et2O was added. The solution was washed with 1N HCl (20 mL), saturated NaHCO3 and then brine, then the organic layer dried over MgSO4, filtered and concentrated to give Intermediate 11A (15.8 g, 68.9 mmol, 89.0% yield) as a white crystalline solid. HPLC/MS (Method L) RT=1.58 min, [M+H]+ 230.0. A white solid precipitated instantly The solvent was evaporated Et2O was added The solution was washed with 1N HCl (20 mL), saturated NaHCO3 brine, then the organic layer dried over MgSO4 filtered concentrated

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

Procedure: To a stirred solution of triphenylphosphine (629 mg, 2.40 mmol) and Intermediate 11A (458 mg, 2.00 mmol) in ClCH2CH2Cl (1 mL) was added dimethyl but-2-ynedioate (0.26 mL, 2.1 mmol) drop wise at rt. The reaction mixture was stirred at 80° C. in a capped vial for 18 h. The reaction mixture was allowed to cool to rt, loaded on to a 40 g silica gel column and purified with 0-100% EtOAc/Hex to give Intermediate 11B (560 mg, 1.58 mmol, 79.0% yield) as a slightly tan viscous oil. HPLC/MS (Method L) RT=1.77 min, [M+H]+ 356.0. to cool to rt purified with 0-100% EtOAc/Hex

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

Procedure: To a solution of 2,4-difluoroaniline (10 g, 77 mmol) and triethylamine (12.95 mL, 93.00 mmol) in THF (50 mL) was added ethyl 2-chloro-2-oxoacetate (9.05 mL, 81.0 mmol) drop wise at 0° C. A white solid precipitated instantly. The reaction mixture was stirred at rt for 1 h. The solvent was evaporated, and Et2O was added. The solution was washed with 1N HCl (20 mL), saturated NaHCO3 and then brine, then the organic layer dried over MgSO4, filtered and concentrated to give Intermediate 11A (15.8 g, 68.9 mmol, 89.0% yield) as a white crystalline solid. HPLC/MS (Method L) RT=1.58 min, [M+H]+ 230.0. A white solid precipitated instantly The solvent was evaporated Et2O was added The solution was washed with 1N HCl (20 mL), saturated NaHCO3 brine, then the organic layer dried over MgSO4 filtered concentrated