反应详情

温度

0 °C

A solution of 0.304 g (1.51 mmol) of 4-nitrophenyl chloroformate dissolved in 5 mL of 1,2-dichloroethane is added dropwise to a solution containing 0.284 g (1.66 mmol) of ethyl 5-hydroxymethylisoxazole-3-carboxylate and 0.39 g (3.02 mmol) of N,N-diisopropylethylamine in 10 mL of 1,2-dichloroethane, cooled to about 0° C. Stirring is continued at 0° C. for 1 hour and then at room temperature for 1 hour. 0.39 g (3.02 mmol) of N,N-diisopropylethylamine and then 0.34 g (1.51 mmol) of tert-butyl 2-amino-6-azaspiro[3.4]octane-6-carboxylate, prepared in step 6.4., are added. The reaction medium is stirred at 70° C. for 4 hours. It is allowed to cool to room temperature. Water is added to the reaction medium, the aqueous phase is separated out and extracted several times with dichloromethane, the combined organic phases are washed with aqueous sodium hydroxide solution (1N) and then with saturated aqueous ammonium chloride solution and dried over sodium sulfate, and the filtrate is concentrated under reduced pressure. 0.44 g of pure product is thus obtained in the form of an orange oil, which is used without further purification in the following step.

1. additionis added dropwise to a solution
2. waitat room temperature for 1 hour
3. addition, are added
4. stirringThe reaction medium is stirred at 70° C. for 4 hours
5. temperatureto cool to room temperature
6. customthe aqueous phase is separated out
7. extractionextracted several times with dichloromethane
8. washthe combined organic phases are washed with aqueous sodium hydroxide solution (1N)
9. dry with materialwith saturated aqueous ammonium chloride solution and dried over sodium sulfate
10. concentrationthe filtrate is concentrated under reduced pressure