反应详情

温度

-20 °C

5.1 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid and 5.7 ml of N-methylmorpholine are cooled in 200 ml of tetrahydrofuran, with stirring, to −20° C. 3.15 ml of chloroformic acid isobutyl ester are added dropwise thereto. Stirring is then carried out for 30 min, during which the reaction temperature is increased to −10° C. Cooling is then carried out to −20° C. again and 5.0 g of 2-(4-hydroxy-3-methoxyphenyl)-ethylamine hydrochloride are introduced. The reaction mixture is allowed to warm to room temperature and is stirred for a further 24 hours. The reaction mixture is introduced into 300 ml of 2N hydrochloric acid. It is extracted twice with 500 ml of ethyl acetate each time. The organic phases are washed twice with 100 ml of saturated sodium chloride solution each time, combined, dried over magnesium sulfate and concentrated. The residue is purified by flash-chromatography on silica gel using a mixture of ethyl acetate/n-hexane 3:1, yielding (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-amide in the form of a colourless oil.

1. stirringStirring
2. temperaturethe reaction temperature is increased to −10° C
3. temperatureCooling
4. customis then carried out to −20° C.
5. temperatureto warm to room temperature
6. stirringis stirred for a further 24 hours
7. extractionIt is extracted twice with 500 ml of ethyl acetate each time
8. washThe organic phases are washed twice with 100 ml of saturated sodium chloride solution each time
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customThe residue is purified by flash-chromatography on silica gel using
12. additiona mixture of ethyl acetate/n-hexane 3:1