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

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 extracted with ethyl acetate. After the obtained organic layer was washed with saturated brine, the layer was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, methylene chloride was added thereto, and 332 mg (1.73 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added thereto under ice-cooling. 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.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. stirringAfter the mixture was stirred at room temperature overnight
3. customthe toluene layer was separated
4. extractionextracted with ethyl acetate
5. washAfter the obtained organic layer was washed with saturated brine
6. dry with materialthe layer was dried with anhydrous sodium sulfate
7. distillationThe solvent was distilled off under reduced pressure, methylene chloride
8. additionwas added
9. temperatureunder ice-cooling
10. stirringAfter the mixture was stirred at room temperature overnight
11. concentrationthe reaction solution was concentrated under reduced pressure, ethyl acetate
12. additionwas added
13. washthe mixture was successively washed with water
14. dry with materialby drying with anhydrous sodium sulfate
15. distillationThe solvent was distilled off under reduced pressure

ORD record

ord-b75fff1a0e5a43f39cbca63867eaa429

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08957205B2