ethyl 3-(4-chloroanilino)-3-oxopropanoate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: Potassium ethyl malonate (3.2 g), 1-hydroxybenzotriazole (2.1 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.5 g) were successively added to a solution of 4-chloroaniline (2.0 g) in N,N-dimethylformamide (20 ml) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate, a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (4.0 g). washed with a saturated aqueous solution of sodium hydrogencarbonate After the resultant organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure

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

Procedure: Potassium ethyl malonate (3.2 g), 1-hydroxybenzotriazole (2.1 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.5 g) were successively added to a solution of 4-chloroaniline (2.0 g) in N,N-dimethylformamide (20 ml) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate, a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (4.0 g). washed with a saturated aqueous solution of sodium hydrogencarbonate After the resultant organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To the stirred solution of benzyne precursor 1 (100 mg, 0.33 mmol) and malonamide ester 2 (40 mg, 0.16 mmol) in anhydrous MeCN (2 mL) was added NaHCO3 (28 mg, 0.33 mmol), CsF (200 mg, 1.34 mmol). Reaction mixture was allowed to stir at room temperature 30° C. for 48 hrs. The reaction mixture was concentrated in vacuo and directly loaded on silica gel and purified by using gradient solvent combination of ethyl acetate/Pet ether to yield a low melting solid compound 4 (43 mg, 65%). Reaction mixture The reaction mixture was concentrated in vacuo purified

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

Procedure: The present invention further provides one pot process for C-arylation of ethyl 3-(4-chlorophenylamino)-3-oxo-propanoate (2) using benzyne precursor (1) in presence of CsF and CH3CN to obtain ethyl 3-(4-chlorophenylamino)-3-oxo-2,2-diphenylpropanoate (4) with more than 85% yield (cf scheme 3).

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

Procedure: To a solution of 4-chloroaniline (2.0 g) in N,N-dimethylformamide (20 mL) were sequentially added at room temperature potassium ethyl malonate (3.2 g), 1-hydroxybenzotriazole (2.1 g), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.5 g), followed by stirring at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with saturated aqueous sodium hydrogencarbonate, 10% aqueous citric acid, and saturated brine. The organic layer was dried over sodium sulfate anhydrate, and the solvent was distilled away under reduced pressure, to thereby give the title compound (4.0 g). washed with saturated aqueous sodium hydrogencarbonate, 10% aqueous citric acid, and saturated brine The organic layer was dried over sodium sulfate anhydrate the solvent was distilled away under reduced pressure

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

Procedure: Potassium ethyl malonate (3.2 g), 1-hydroxy-benzotriazole (2.1 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. (4.5 g) were successively added to a solution of 4-chloroaniline (2.0 g) in N,N-dimethylformamide (20 ml) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate, a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (4.0 g). washed with a saturated aqueous solution of sodium hydrogencarbonate After the resultant organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure

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

Procedure: Potassium ethyl malonate (3.2 g), 1-hydroxybenzotriazole (2.1 g) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.5 g) were successively added to a solution of 4-chloroaniline (2.0 g) in N,N-dimethylformamide (20 ml) at room temperature, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous solution of sodium hydrogencarbonate, a 10% aqueous solution of citric acid and saturated aqueous solution of sodium chloride. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain the title compound (4.0 g). washed with a saturated aqueous solution of sodium hydrogencarbonate After the resultant organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir: