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 are cooled in 450 ml of tetrahydrofuran, with stirring, to −20° C. 13.2 ml of chloroformic acid isobutyl ester are added dropwise thereto over 10 min and the reaction mixture is subsequently stirred for 1 hour at −10° C. It is then 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 over 20 min. The reaction mixture is then stirred for 4 hours without cooling, the internal temperature gradually rising to room temperature. The reaction mixture is introduced into 400 ml of 2N hydrochloric acid and extracted twice with 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 with 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)-3-methyl-butyric acid N-[2-(4-benzyloxy-3-methoxyphenyl)-ethyl]-amide, which can be purified by recrystallisation from tert-butyl methyl ether, m.p. 140-142° C.

1. stirringthe reaction mixture is subsequently stirred for 1 hour at −10° C
2. temperatureIt is then cooled to −20° C.
3. stirringThe reaction mixture is then stirred for 4 hours
4. temperaturewithout cooling
5. customgradually rising to room temperature
6. extractionextracted twice with 500 ml of ethyl acetate each time
7. washThe organic phases are washed once with 250 ml of 2N hydrochloric acid, once with 250 ml of saturated sodium chloride solution, twice with 250 ml of 2N potassium hydrogen carbonate solution each time
8. dry with materialonce with 250 ml of saturated sodium chloride solution, dried over magnesium sulfate
9. concentrationconcentrated

ORDレコード

ord-1a28baf5936346f6858f6be57ec549c7

出典データセット

uspto-grants-2001_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06194611B1