Hydrochloric Acid → HCID 86680203, compound

Temperature

0 °C

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.

1. additionwere added at 0° C
2. customat RT
3. customovernight
4. temperaturethe reaction solution was warmed to 50° C
5. stirringthe mixture was stirred at 60° C. for a further 12 h
6. extractionThe aqueous phase was extracted three times with ethyl acetate
7. dry with materialThe combined organic phases were dried over magnesium sulphate
8. concentrationconcentrated under reduced pressure

ORD record

ord-d11cfe1121b84d3da6704127d38e0eda

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796335B2