Hydrochloric Acid → (S)-2-(Ethylsulfonylamino)-3-methyl-butyric acid N-[2-(4-hydroxy-3-methoxyphenyl)-ethyl]-amide

Temperature

-20 °C

5.1 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid and 5.7 ml of N-methylmorpholine in 200 ml of tetrahydrofuran are cooled, with stirring, to −20° C. 3.15 ml of isobutyl chloroformate are added dropwise thereto. When the addition is complete, the reaction mixture is stirred at −10° C. for 40 minutes. The mixture is again cooled to −20° C. 5.0 g of solid 2-(4-hydroxy-3-methoxy-phenyl)-ethylamine hydrochloride are introduced into the reaction mixture. The reaction mixture is stirred, without cooling, for a further 24 hours, the internal temperature gradually rising to room temperature. The reaction mixture is introduced into 300 ml of 2N hydrochloric acid. Extraction is carried out twice using 500 ml of ethyl acetate each time. The organic phases are washed twice using 100 ml of saturated sodium chloride solution each time, dried over magnesium sulfate and concentrated. The residue is purified by flash chromatography on silica gel with a mixture of ethyl acetate/n-hexane 3: 1, yielding (S)-2-(ethylsulfonylamino)-3methyl-butyric acid N-[2-(4-hydroxy-3-methoxyphenyl)-ethyl]-amide in the form of a colourless oil.

1. additionWhen the addition
2. stirringthe reaction mixture is stirred at −10° C. for 40 minutes
3. temperatureThe mixture is again cooled to −20° C
4. stirringThe reaction mixture is stirred
5. temperaturewithout cooling, for a further 24 hours
6. customgradually rising to room temperature
7. extractionExtraction
8. washThe organic phases are washed twice
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated
11. customThe residue is purified by flash chromatography on silica gel with a mixture of ethyl acetate/n-hexane 3: 1

ORD record

ord-b962dc1729c24ee3b0df2e9774fa2363

Source dataset

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06277849B1