反应详情

Treat a mixture of 3′,5′-dichloro-4′-[(R)-2-oxo-cis-1-(4-triisopropylsilanyloxy-cyclohexyl)-pyrrolidin-3-ylmethyl]-biphenyl-4-carboxylic acid (4 g, 5.46 mmol), 1-(2-fluoro-ethyl)-piperazine (2.97 g, 12.12 mmol) and diisopropylethylamine (3.13 g, 24.24 mmol) in 125 mL dichloromethane with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.1 g, 16.16 mmol) and stir at room temperature overnight. Dilute with 150 mL saturated sodium bicarbonate and separate layers. Wash the organic layer with 150 mL water then 100 mL brine. Extract the combined aqueous layers with 100 mL dichloromethane and combine with original organic layer. Dry over sodium sulfate, filter, concentrate, and purify via silica chromatography to give 4 g (67%) product as a foam: MS (m/z): 732 (M+).

1. additionTreat
2. customseparate layers
3. washWash the organic layer with 150 mL water
4. extractionExtract the combined aqueous layers with 100 mL dichloromethane
5. dry with materialDry over sodium sulfate
6. filtrationfilter
7. concentrationconcentrate
8. custompurify via silica chromatography