dihydro-3-methyl-2H-pyran-2,6(3H)-dione

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-methyldihydro-2H-pyran-2,6(3H)-dione (876 mg, 6.84 mmol), 4-amino-2-chlorobenzonitrile (1044 mg, 6.84 mmol) and TEA (0.953 mL, 6.84 mmol) in toluene (10 mL) was stirred at 70° C. for 3 hr. To the reaction mixture was added brine at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) to give a mixture (750 mg, 2.67 mmol, 39.1%) of 5-((3-chloro-4-cyanophenyl)amino)-2-methyl-5-oxopentanoic acid and 5-((3-chloro-4-cyanophenyl)amino)-4-methyl-5-oxopentanoic acid, as a colorless powder. the mixture was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of 3-methyldihydro-2H-pyran-2,6(3H)-dione (876 mg, 6.84 mmol), 4-amino-2-chlorobenzonitrile (1044 mg, 6.84 mmol) and TEA (0.953 mL, 6.84 mmol) in toluene (10 mL) was stirred at 70° C. for 3 hr. To the reaction mixture was added brine at room temperature, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried, and the solvent was evaporated under reduced pressure. The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane) to give a mixture (750 mg, 2.67 mmol, 39.1%) of 5-((3-chloro-4-cyanophenyl)amino)-2-methyl-5-oxopentanoic acid and 5-((3-chloro-4-cyanophenyl)amino)-4-methyl-5-oxopentanoic acid, as a colorless powder. the mixture was extracted with ethyl acetate The organic layer was washed with water and saturated brine dried the solvent was evaporated under reduced pressure The obtained residue was purified by COOH-silica gel column chromatography (solvent gradient; 10 to 100% ethyl acetate/hexane)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The starting materials for said compounds 1, 2, 4, 6, 11 and 12 are the 3-carbomethoxy-2-methylpropanoyl chloride, 2-methylglutaric anhydride, 4-carbomethoxy-2-methylbutanoyl chloride, 3-methylglutaric anhydride and the erythro or threo 4-carbomethoxy-4-(2-phenethyl)-2-methylbutanoyl chloride respectively. That of compound 8 and 9 may be prepared as follows: The solution of 6.0 of meso-2,4-dimethylglutaric acid anhydride [J. Am. Chem. Soc. 77, 1862 (1955)] in 4 ml of methanol is refluxed for one hour and evaporated, to yield the erythro 4-carbomethoxy-2,4-dimethylbutanoic acid. It is converted into the acid chloride by refluxing it with 10.9 g of oxalyl chloride in 50 ml of methylene chloride for 2 hours, and evaporating said mixture. evaporated