1-Aminocyclohexanecarboxylic acid → 2-(5-Methylisoxazol-4-yl)-3-oxa-1-azaspiro[4.5]dec-1-en-4-one

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Reaction Steps

1 g (7.87 mmol) of 5-methylisoxazole-4-carboxylic acid was added to 3 ml of thionyl chloride, and the mixture was stirred overnight. The reaction solution was concentrated under reduced pressure and the obtained residue was added to a solution of 1.13 g (7.87 mmol) of 1-aminocyclohexanecarboxylic acid and 6.6 g (79 mmol) of sodium hydrogencarbonate in 30 ml of toluene-30 ml of water. After the mixture was stirred at room temperature overnight, the toluene layer was separated. The aqueous layer was neutralized by potassium hydrogensulfate, and it was extracted with ethyl acetate. After the obtained organic layer was washed with saturated brine, it was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, methylene chloride was added thereto, and under ice-cooling, 332 mg (1.73 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added. After the mixture was stirred at room temperature overnight, the reaction solution was concentrated under reduced pressure, ethyl acetate was added thereto, and the mixture was successively washed with water, a 10% aqueous potassium hydrogensulfate solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, followed by drying with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 295 mg (16%) of the title compound.

Provenance & Evidence