methyl 3-oxocycloheptane-1-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.4 g (0.02 mol) of methyl 3-oxocycloheptanecarboxylate, 1.91 g (0.022 mol) of morpholine and 0.005 g of p-toluenesulfonic acid in 30 ml of dry toluene was heated under reflux for 6 hours in a Dean-Stark apparatus until no additional water was collected. There were then added 2.02 g (0.02 mol) of triethylamine followed by a solution of 3.83 g (0.02.mol) of p-chlorobenzoyl chloride in 20 ml of toluene over a period of 10 minutes at 20° C. The mixture was heated at 60° C. for 6 hours, whereupon the precipitated triethylamine hydrochloride was removed from the cooled solution by filtration and washed with toluene. The combined toluene solutions were evaporated and 1.4 g (0.02 mol) of hydroxylamine hydrochloride dissolved in 10 ml of ethanol and 5 ml of pyridine were added. The mixture was heated under reflux for 2 hours. The solvent was removed by evaporation and an excess of 2N hydrochloric acid was added. The mixture was extracted twice with diethyl ether and the combined extracts were washed with 2N sodium carbonate solution and dried over magnesium sulfate. After evaporation, the resulting syrup was purified by column chromatography on silica gel using hexane/ethyl acetate (2:1) for the elution. There were obtained 1.2 g of methyl 3-(4-chlorophenyl)-5,6,7,8-tetrahydro-4H-cyclohept[c]isoxazole-7- -carboxylate of melting point 94°-95° C. was collected was removed from the cooled solution by filtration washed with toluene The combined toluene solutions were evaporated The mixture was heated under reflux for 2 hours The solvent was removed by evaporation an excess of 2N hydrochloric acid was added The mixture was extracted twice with diethyl ether the combined extracts were washed with 2N sodium carbonate solution dried over magnesium sulfate After evaporation the resulting syrup was purified by column chromatography on silica gel for the elution