Triethylamine → 4-[3-[4-[Bis(4-Fluorophenyl)hydroxymethyl]-1-piperidinyl]-propoxy]-alpha-hydroxy-3-methoxybenzeneacetic acid (phenylmethyl) ester

Participants

Reaction Conditions

Reaction Steps

A mixture of 0.637 g (0.00175 mole) 4-(3-chloropropoxy)-3-methoxymandelic acid phenylmethyl ester, 0.545 g (0.00180 mole) of [α,α-bis(4-fluorophenyl)]-4-piperidinemethanol hydrochloride, and 0.3 ml (0.0025 mole) of triethylamine in 3 ml of benzyl alcohol was heated under nitrogen atmosphere at 110° C. for 7 hours while the reaction was monitored by TLC (silica gel, methylene chloride/methanol/ammonium hydroxide 90:10:1). The reaction mixture was concentrated in vacuo, ethyl ether (60 ml) and hexanes (40 ml) were added to the oily residue, and the solution was kept in the refrigerator for 2 hours. The solid that formed was filtered, washed with ether and dissolved in methylene chloride (40 ml). The methylene chloride solution was washed with water (3×10 ml) and dried (sodium sulfate), and the solvent was evaporated in vacuo to give 0.6 g of an oil. Final purification was done using 6 tapered silica gel plates 20×20 cm eluting with methylene chloride/methanol/ammonium hydroxide (90:5:0.5). The TLC sections containing the product were scraped off, and eluted with the above solvent system to give 0.4 g (34%) of the product as a light-amber oil. 1H NMR and mass spectral analysis support the structure assigned.

Provenance & Evidence