N-[3-(4-Fluorophenyl)-3-oxopropyl]pipecolic acid methyl ester → N-[3-(4-chlorophenyl)-3-(4-fluorophenyl)3-hydroxypropyl]pipecolic acid methyl ester

Participants

Reaction Steps

7 ml (2 mmol) of 0.28 M solution of 4-chlorophenylmagnesium iodide in diethyl ether [prepared from 1-chloro-4-iodobenzene (Aldrich) and magnesium] was added dropwise to an ice-cooled solution of 0.605 g (2 mmol) N-[3-(4-fluorophenyl)-3-oxopropyl]pipecolic acid methyl ester (from Step 1) in 12 ml anhydrous diethyl ether with stirring under nitrogen. The mixture was stirred at room temperature for 16 hours, poured onto crushed ice and extracted with dichloromethane. The combined organic extracts were washed with brine, concentrated and the residue purified by preparative silica gel TLC with 25% ethyl acetate in hexanes to give 0.037 g (yield 4.5%) N-[3-(4-chlorophenyl)-3-(4-fluorophenyl)3-hydroxypropyl]pipecolic acid methyl ester (Compound B30).

Provenance & Evidence