ethyl 3-(2-chlorophenyl)-3-oxopropanoate

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

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

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

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

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

Procedure: Sodium hydride (8.7 grams) and 21.4 grams of diethyl carbonate are suspended in 100 ml of tetrahydrofuran, 14 grams of o-chloroacetophenone is gradually dropped thereinto by keeping the inner temperature at 40° to 50° C., then a small amount of ethanol is added thereto and heated to reflux for four hours. After cooling, 20 ml of ethanol is added thereto, the mixture is poured into ice water, and extracted with ether. Ether extracts are combined, washed with water, dried with anhydrous magnesium sulfate, and ether is evaporated therefrom. The resulting oil is purified by distillation in vacuo to give 8.8 grams of colorless, oily product, b.p. 120° to 125° C./1 mmg Hg. at 40° to 50° C. heated to reflux for four hours After cooling extracted with ether washed with water dried with anhydrous magnesium sulfate, and ether is evaporated The resulting oil is purified by distillation in vacuo to give 8.8 grams of colorless, oily product, b.p. 120° to 125° C./1 mmg Hg

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

Procedure: The title compound was prepared in 75% yield from 2-hydrazinylpyridine-4-carbonitrile (PREPARATION 2) and ethyl 3-(2-chlorophenyl)-3-oxopropanoate according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C15H9ClN4O 297; Found, 297.

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (1.45 g, 36 mmol) and diethyl carbonate (2.14 g, 18 mmol) were suspended in 10 ml of THF. 1-(2-Chlorophenyl)ethanone (1.4 g, 9 mmol) was gradually added into the reaction flask, maintaining the reaction mixture temperature at 40° C. for 2 h. Then 1 mL of ethanol was added thereto and heated under reflux conditions for 4 h. After cooling, 1 mL of ethanol was added and the mixture was poured onto ice water, and extracted with ether. Ether extracts are combined, washed with water, dried with anhydrous magnesium sulfate, and evaporated. The resulting oil is purified by flash column chromatography (PE/EA=50/1) to afford the title compound (680 mg, 34%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 1.24 (3H, t, J=6.8 Hz), 4.03 (2H, s), 4.19 (2H, q, J=6.8 Hz), 7.31-7.36 (2H, m), 7.42-7.45 (2H, m). [M+H] Calc'd for C11H11ClO3, 227; Found, 227. heated under reflux conditions for 4 h After cooling the mixture was poured onto ice water extracted with ether washed with water dried with anhydrous magnesium sulfate evaporated The resulting oil is purified by flash column chromatography (PE/EA=50/1)

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

Procedure: The title compound was prepared in 75% yield from 2-hydrazinylpyridine-4-carbonitrile (PREPARATION 2) and ethyl 3-(2-chlorophenyl)-3-oxopropanoate according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C15H9ClN4O 297. Found, 297.

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

Procedure: The title compound was prepared in 75% yield from 2-hydrazinylpyridine-4-carbonitrile (PREPARATION 2) and ethyl 3-(2-chlorophenyl)-3-oxopropanoate according to the procedure for the preparation of Example 3, part A. [M+H] Calc'd for C15H9ClN4O 297. Found, 297.

Conditions: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium hydride (1.45 g, 36 mmol) and diethyl carbonate (2.14 g, 18 mmol) were suspended in 10 ml of THF. 1-(2-Chlorophenyl)ethanone (1.4 g, 9 mmol) was gradually added into the reaction flask, maintaining the reaction mixture temperature at 40° C. for 2 h. Then 1 mL of ethanol was added thereto and heated under reflux conditions for 4 h. After cooling, 1 mL of ethanol was added and the mixture was poured onto ice water, and extracted with ether. Ether extracts are combined, washed with water, dried with anhydrous magnesium sulfate, and evaporated. The resulting oil is purified by flash column chromatography (PE/EA=50/1) to afford the title compound (680 mg, 34%) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 1.24 (3H, t, J=6.8 Hz), 4.03 (2H, s), 4.19 (2H, q, J=6.8 Hz), 7.31-7.36 (2H, m), 7.42-7.45 (2H, m). [M+H] Calc'd for C11H11ClO3, 227. Found, 227. heated under reflux conditions for 4 h After cooling the mixture was poured onto ice water extracted with ether washed with water dried with anhydrous magnesium sulfate evaporated The resulting oil is purified by flash column chromatography (PE/EA=50/1)

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

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

Procedure: To a stirred solution of 3-(2-chloro-phenyl)-3-oxo-propionicacidethylester (5.000 mL, 26.600 mmol) in ether (75.00 mL) was added dropwise sulfuryl chloride (2.800 mL, 34.600 mmol) and the resulting solution was stirred for 4 h. The reaction mixture was diluted with ether (50.0 mL) and quenched by the slow addition of a saturated aqueous solution of sodium bicarbonate (50.0 mL) and the mixture was vigorously stirred for 30 min. The organic phase was separated and dried over anhydrous MgSO4, filtered, and concentrated in vacuo to provide 6.500 g of crude product as a clear colorless oil (100%). The crude residue was used without further purification. LC/MS (AA) ES+ 261, 263. 1H NMR (400 MHz, d, CDCl3) δ: 12.47 (s, 1H), 7.49-7.32 (m, 4H), 4.39 (q, J=7.2 Hz, 2H), 1.41 (t, J=7.2 Hz, 3H). quenched by the slow addition of a saturated aqueous solution of sodium bicarbonate (50.0 mL) the mixture was vigorously stirred for 30 min The organic phase was separated dried over anhydrous MgSO4 filtered concentrated in vacuo