dimethyl 2-diazo-3-oxopentanedioate

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

Procedure: To a mixture of 3-ketoglutaric acid dimethyl ester 15.0 g, triethylamine 9.6 g and acetonitrile 300 ml is portionwise added 4-acetylaminobenzensulfonylazide 20.7 g at 0° C. The mixture is stirred at room temperature for 30 minutes. After removal of the precipitate by filtration the filtrate is concentrated in vacuo. The residue is diluted with a mixture of hexane and diethyl ether (1:1). The insoluble materials are removed by filtration and the filtrate is concentrated in vacuo. The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1) to give 2-diazo-3-ketoglutaric acid dimethyl ester as a pale yellow oil, 16.03 g. at 0° C After removal of the precipitate by filtration the filtrate is concentrated in vacuo The residue is diluted with a mixture of hexane and diethyl ether (1:1) The insoluble materials are removed by filtration the filtrate is concentrated in vacuo The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1)

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

Procedure: To a mixture of 3-ketoglutaric acid dimethyl ester 15.0 g, triethylamine 9.6 g and acetonitrile 300 ml is portionwise added 4-acetylaminobenzensulfonylazide 20.7 g at 0° C. The mixture is stirred at room temperature for 30 minutes. After removal of the precipitate by filtration the filtrate is concentrated in vacuo. The residue is diluted with a mixture of hexane and diethyl ether (1:1). The insoluble materials are removed by filtration and the filtrate is concentrated in vacuo. The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1) to give 2-diazo-3-ketoglutaric acid dimethyl ester as a pale yellow oil, 16.03 g. at 0° C After removal of the precipitate by filtration the filtrate is concentrated in vacuo The residue is diluted with a mixture of hexane and diethyl ether (1:1) The insoluble materials are removed by filtration the filtrate is concentrated in vacuo The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1)

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

Procedure: A mixture of 2-diazo-3-oxo-pentanedioic acid dimethyl ester (50.0 g, 249.8 mmol) and triphenylphosphine (65.5 g, 249.8 mmol) in diethyl ether (500 mL) was stirred at room temperature for 24 h. The organic solvent was removed under vacuum and then acetic acid (500 mL) and water (50 mL) were added to the residue and the mixture was refluxed for 10 h. The reaction mixture was concentrated under reduced pressure to obtain a viscous residue. Trituration with ethyl acetate generated a yellow solid that was purified by chromatography (silica, 100-200 mesh, 1-5% methanol in dichloromethane) to give 4,6-dihydroxy-pyridazine-3-carboxylic acid methyl ester (12.8 g, 30%) as a yellow solid. LC-MS 169.2 [M+H]+. The organic solvent was removed under vacuum acetic acid (500 mL) and water (50 mL) were added to the residue the mixture was refluxed for 10 h The reaction mixture was concentrated under reduced pressure to obtain a viscous residue that was purified by chromatography (silica, 100-200 mesh, 1-5% methanol in dichloromethane)

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

Procedure: To a stirred solution of dimethyl 3-oxopentanedioate (50.0 g, 287.1 mmol) and triethylamine (47.8 mL, 344.5 mmol) in acetonitrile (1.2 L) at 0° C. was added 4-acetamidobenzene sulfonyl azide (69.0 g, 287.1 mmol) portion wise. After addition was completed, the reaction mixture was stirred at room temperature for 1 h (silica TLC; ethyl acetate:hexane=1:4, Rf=0.3; showed KMnO4 activity). The reaction mixture was filtered, and the filtrate was concentrated to get a viscous mass, which was diluted with n-hexane (3 L). The unwanted solid byproduct was removed by filtration then filtrate was concentrated under reduced pressure to give 2-diazo-3-oxo-pentanedioic acid dimethyl ester (50.0 g, 87% crude yield) as a light yellow liquid, which was directly used for next step without further purification. After addition The reaction mixture was filtered the filtrate was concentrated to get a viscous mass, which The unwanted solid byproduct was removed by filtration filtrate was concentrated under reduced pressure

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

Procedure: To a mixture of 3-ketoglutaric acid dimethyl ester 15.0 g, triethylamine 9.6 g and acetonitrile 300 ml is portionwise added 4-acetylaminobenzensulfonylazide 20.7 g at 0° C. The mixture is stirred at room temperature for 30 minutes. After removal of the precipitate by filtration the filtrate is concentrated in vacuo. The residue is diluted with a mixture of hexane and diethyl ether (1:1). The insoluble materials are removed by filtration and the filtrate is concentrated in vacuo. The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:1→3:1) to give 2-diazo-3-ketoglutaric acid dimethyl ester as a pale yellow oil, 16.03 g. at 0° C After removal of the precipitate by filtration the filtrate is concentrated in vacuo The residue is diluted with a mixture of hexane and diethyl ether (1:1) The insoluble materials are removed by filtration the filtrate is concentrated in vacuo The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:1→3:1)

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

Procedure: To a mixture of 3-ketoglutaric acid dimethyl ester 15.0 g, triethylamine 9.6 g and acetonitrile 300 ml is portionwise added 4-acetylaminobenzensulfonylazide 20.7 g at 0° C. The mixture is stirred at room temperature for 30 minutes. After removal of the precipitate by filtration the filtrate is concentrated in vacuo. The residue is diluted with a mixture of hexane and diethyl ether (1:1). The insoluble materials are removed by filtration and the filtrate is concentrated in vacuo. The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1) to give 2-diazo-3-ketoglutaric acid dimethyl ester as a pale yellow oil, 16.03 g. at 0° C After removal of the precipitate by filtration the filtrate is concentrated in vacuo The residue is diluted with a mixture of hexane and diethyl ether (1:1) The insoluble materials are removed by filtration the filtrate is concentrated in vacuo The residue is purified with column chromatography (silica gel 225 g, solvent; hexane:ethyl acetate=5:13:1)