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

温度

-20 °C

21.1 g of (S)-2-(ethylsulfonylamino)-3-methyl-butyric acid and 12 ml of N-methylmorpholine in 450 ml of tetrahydrofuran are cooled, with stirring, to −20° C. 13.2 ml of isobutyl chloroformate are added dropwise thereto over a period of 10 minutes. The reaction mixture is then stirred at −10° C. for 1 hour. The mixture is again cooled to −20° C., and a solution of 26.1 g of 2-(4-benzyloxy-3-methoxyphenyl)-ethylamine in 100 ml of tetrahydrofuran is added dropwise thereto over a period of 20 minutes. The reaction mixture is then stirred, without cooling, for 4 hours, the internal temperature gradually rising to room temperature. The reaction mixture is then introduced into 400 ml of 2N hydrochloric acid. Extraction is carried out twice using 500 ml of ethyl acetate each time. The organic phases are washed once with 250 ml of 2N hydrochloric acid, once with 250 ml of saturated sodium chloride solution, twice using 250 ml of 2N potassium hydrogen carbonate solution each time and once with 250 ml of saturated sodium chloride solution, dried over magnesium sulfate and concentrated, yielding (S)-2-(ethylsulfonylamino)-3methyl-butyric acid N-[2-(4-benzyloxy-3-methoxy-phenyl)-ethyl]-amide, m.p. 140-142° C., which can be purified further by digestion in 200 ml of tert-butyl methyl ether.

1. stirringThe reaction mixture is then stirred at −10° C. for 1 hour
2. temperatureThe mixture is again cooled to −20° C.
3. waitover a period of 20 minutes
4. stirringThe reaction mixture is then stirred
5. temperaturewithout cooling, for 4 hours
6. customgradually rising to room temperature
7. extractionExtraction
8. washThe organic phases are washed once with 250 ml of 2N hydrochloric acid, once with 250 ml of saturated sodium chloride solution
9. dry with materialonce with 250 ml of saturated sodium chloride solution, dried over magnesium sulfate
10. concentrationconcentrated

ORDレコード

ord-0a25d69121614118a3a673d9a72783fc

出典データセット

uspto-grants-2001_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06277849B1