반응 #2489548

반응 방정식

hydrochloric acid

ethyl 3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropyl-2-methylpropanoate

lithium hydroxide monohydrate

lithium hydroxide monohydrate

→

3-(4-Chloro-3-{[(3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropyl-2-methylpropanoic acid

용매

water

methanol

THF

water

methanol

반응 조건

후처리

1. 1
   workup.ADDITIONwere added at 0° C
2. 2
   기타at RT
3. 3
   기타overnight
4. 4
   온도the reaction solution was warmed to 50° C
5. 5
   workup.STIRRINGthe mixture was stirred at 60° C. for a further 12 h
6. 6
   추출The aqueous phase was extracted three times with ethyl acetate
7. 7
   건조The combined organic phases were dried over magnesium sulphate
8. 8
   농축concentrated under reduced pressure

실험 절차

250 mg (0.47 mmol) of ethyl 3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropyl-2-methylpropanoate (diastereomer mixture; Example 129A) were dissolved in a mixture of 1.0 ml of methanol, 0.5 ml of THF and 0.5 ml of water, and 40 mg (0.94 mmol) of lithium hydroxide monohydrate were added at 0° C. The mixture was stirred initially at 0° C. for 1 h and then at RT overnight. Another 40 mg (0.94 mmol) of lithium hydroxide monohydrate were then added, and the reaction solution was warmed to 50° C. After further stirring at this temperature overnight, 1 ml of methanol was metered into the reaction mixture, and the mixture was stirred at 60° C. for a further 12 h. The solution was then diluted with water and acidified with 1 N hydrochloric acid (pH about 2). The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over magnesium sulphate and concentrated under reduced pressure. This gave 204 mg (86% of theory) of the title compound as a diastereomer mixture.

출처