ethyl 4-(2,4-dichlorophenyl)-2,4-dioxobutanoate

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

Procedure: Starting from 1 g (3.46 mmol) of 4-(2,4-dichlorophenyl)-2,4-dioxobutanoic acid ethyl ester from example 11A and 842.25 mg (4.7 mmol) of 3-chlorophenylhydrazine hydrochloride, 297.5 mg (0.75 mmol, 22% yield of theory) of product are obtained according to the method described in example 4A and after purification by preparative HPLC. are obtained after purification by preparative HPLC

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 20% sodium ethoxide-ethanol solution (17 g) was added to tetrahydrofuran (100 ml), and the mixture was cooled to 0° C. It took 60 minutes to dropwise add a solution of 2′,4′-dichloroacetophenone (9.45 g) and diethyl oxalate (7.30 g) in tetrahydrofuran (100 ml) to the mixture. After the completion of the dropping, the mixture was allowed to warm to a room temperature and stirred for 2 hours. To the mixture, 2-N hydrochloric acid (200 ml) and chloroform (200 ml) were added. The organic layer was collected by separation and dried over anhydrous magnesium sulfate, and the solvent was distilled off. Thus, the title compound (11.3 g, 78%) as a light-brown oily substance was obtained. to warm to a room temperature The organic layer was collected by separation dried over anhydrous magnesium sulfate the solvent was distilled off

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

Procedure: Intermediate (1) (15.4 g) was dissolved in acetic acid and sodium nitrite (3.8 g) in 15 ml water was added slowly. After the exothermic reaction was complete, and the reaction mixture began to cool, methyl hydrazine (6 ml) was added. The reaction mixture was allowed to stir overnight, or until the mixture became yellow. The mixture was concentrated to dryness, giving a yellow oil. This oil was suspended between ether and 2N HCl. The aqueous solution was separated and neutralized with sodium bicarbonate and the slightly basic solution was extracted with ethyl acetate. The ethyl acetate layer was dried and concentrated, yielding 1-methyl-3-carboxyethyl-4-amino-5-(2,4-dicliloroplienyl)pyrazole (intermediate 2), which was used without purification in the next step. After the exothermic reaction to cool The mixture was concentrated to dryness giving a yellow oil The aqueous solution was separated the slightly basic solution was extracted with ethyl acetate The ethyl acetate layer was dried concentrated

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,4-dichloroacetophenone (3.78 g) in THF (20 ml) was cooled to −78° C. under a nitrogen atmosphere. To this stirred solution was added lithium diisopropylamide (LDA) (1.0 M, 22 ml) and the resulting solution was stirred at −78° C. for 15 minutes. Acetoxyacetyl chloride (2.3 ml) was injected and the mixture was stirred for 1 hour and then allowed to warm to room temperature. The reaction was quenched with 1N HCl and the product was extracted with diethyl ether (200 ml). The organic layer was dried, concentrated and recrystallized from ether/hexanes, yielding ethyl 4-(2,4-dichlorophenyl)-2,4-diketobutyrate (intermediate 1). the mixture was stirred for 1 hour to warm to room temperature The reaction was quenched with 1N HCl the product was extracted with diethyl ether (200 ml) The organic layer was dried concentrated recrystallized from ether/hexanes