methyl 4-methyl-2-oxopentanoate

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid methyl ester (3.8 g, 26 mmol) in N,N-dimethylformamide dimethyl acetal (7 mL, 52 mmol) is added p-toluenesulfonic acid monohydrate (30 mg) and the mixture is stirred at 80° C. overnight. The reaction mixture is concentrated under reduced pressure to give 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester as an orange oil. To a solution of 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester and 2,6-dichlorophenylhydrazine hydrochloride (2.8 g, 13 mmol) in EtOH (40 mL) is added concentrated HCl (0.5 mL). The mixture is stirred at ambient temperature for 2 h followed by refluxing overnight. The reaction mixture is concentrated and the residue is partitioned between EtOAc and 1N HCl. The organic phase is dried (Na2SO4) and concentrated to a residue. The residue is purified by column chromatography (0-15% EtOAc in hexanes) to give the title compound as an oil (2.2 g, 52%). 1H NMR (CDCl3): δ 7.76 (s, 1H), 7.43 (d, 2H), 7.34 (dd, 1H), 3.75 (s, 3H), 3.48 (m, 1H), 1.32 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid methyl ester (3.8 g, 26 mmol) in N,N-dimethylformamide dimethyl acetal (7 mL, 52 mmol) is added p-toluenesulfonic acid monohydrate (30 mg) and the mixture is stirred at 80° C. overnight. The reaction mixture is concentrated under reduced pressure to give 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester as an orange oil. To a solution of 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester and 2,6-dichlorophenylhydrazine hydrochloride (2.8 g, 13 mmol) in EtOH (40 mL) is added concentrated HCl (0.5 mL). The mixture is stirred at ambient temperature for 2 h followed by refluxing overnight. The reaction mixture is concentrated and the residue is partitioned between EtOAc and 1N HCl. The organic phase is dried (Na2SO4) and concentrated to a residue. The residue is purified by column chromatography (0-15% EtOAc in hexanes) to give the title compound as an oil (2.2 g, 52%). 1H NMR (CDCl3): δ 7.76 (s, 1H), 7.43 (d, 2H), 7.34 (dd, 1H), 3.75 (s, 3H), 3.48 (m, 1H), 1.32 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid (3.4 g, 26 mmol) in methanol (12 mL) and 2,2-dimethoxypropane (48 mL) is added chlorotrimethylsilane (0.38 mL). The reaction mixture is stirred at ambient temperature overnight. The reaction mixture is concentrated under reduced pressure to give the title compound as an oil, (3.8 g, quant.). 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 3H), 2.72 (d, 2H), 2.16 (m, 1H), 0.96 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid (3.4 g, 26 mmol) in methanol (12 mL) and 2,2-dimethoxypropane (48 mL) is added chlorotrimethylsilane (0.38 mL). The reaction mixture is stirred at ambient temperature overnight. The reaction mixture is concentrated under reduced pressure to give the title compound as an oil, (3.8 g, quant.). 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 3H), 2.72 (d, 2H), 2.16 (m, 1H), 0.96 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid (3.4 g, 26 mmol) in methanol (12 mL) and 2,2-dimethoxypropane (48 mL) is added chlorotrimethylsilane (0.38 mL). The reaction mixture is stirred at ambient temperature overnight. The reaction mixture is concentrated under reduced pressure to give the title compound as an oil, (3.8 g, quant.). 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 3H), 2.72 (d, 2H), 2.16 (m, 1H), 0.96 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid methyl ester (3.8 g, 26 mmol) in N,N-dimethylformamide dimethyl acetal (7 mL, 52 mmol) is added p-toluenesulfonic acid monohydrate (30 mg). The mixture is stirred at 80° C. overnight. The reaction mixture is concentrated under reduced pressure to give 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester as an orange oil. To a solution of 3-isopropyl-4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester and 2,6-dichlorophenylhydrazine hydrochloride (2.8 g, 13 mmol) in EtOH (40 mL) is added concentrated HCl (0.5 mL). The mixture is stirred at ambient temperature for 2 h followed by refluxing overnight. The reaction mixture is concentrated and the residue is partitioned between EtOAc and 1N HCl. The organic phase is dried (Na2SO4) and concentrated to a residue. The residue is purified by column chromatography (0-15% EtOAc in hexanes) to give the title compound as an oil (2.2 g, 52%). 1H NMR (CDCl3): δ 7.76 (s, 1H), 7.43 (d, 2H), 7.34 (dd, 1H), 3.75 (s, 3H), 3.48 (m, 1H), 1.32 (d, 6H). The reaction mixture is concentrated under reduced pressure

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

Procedure: To a solution of 4-methyl-2-oxo-pentanoic acid (3.4 g, 26 mmol) in methanol (12 mL) and 2,2-dimethoxypropane (48 mL) is added chlorotrimethylsilane (0.38 mL). The reaction mixture is stirred at ambient temperature overnight. The reaction mixture is concentrated under reduced pressure to give the title compound as an oil, (3.8 g, quant.). 1H NMR (400 MHz, CDCl3): δ 3.86 (s, 3H), 2.72 (d, 2H), 2.16 (m, 1H), 0.96 (d, 6H). The reaction mixture is concentrated under reduced pressure