Diisopropylamine → 1-[(4-Methoxyphenyl)methyl]cyclopentanecarboxylic acid ethyl ester

Participants

Reaction Steps

A solution of diisopropylamine (58 mL. 0.44 mol) in THF 400 mL was cooled to below 0° C. and n-butyl lithium in hexane (170 mL, 2.5 N, 0.43 mol) was added dropwise maintaining the temperature below 0° C. Upon completion of the addition, ethyl cyclopentylcarboxylate (55 g, 0.39 mol) in THF (175 mL) was added dropwise maintaining the internal temperature between −60 and −70° C. Upon completion of the addition, the internal temperature was allowed to rise to −40° C. and was held there for 20 min and lowered back to −70° C. A solution of 4-methoxybenzyl bromide (75 g, 0.48 mol) in 175 mL of THF was added dropwise and the mixture was allowed to warm to room temperature overnight. A solution of 20% ammonium chloride in water (225 mL) was added followed by 450 mL of ethyl acetate, the layers were separated, the aqueous layer was extracted with ethyl acetate (450 mL) and the combined organic layers were washed with saturated brine (2×450 mL) and were dried (MgSO4). The crude product was chromatographed on silica gel, eluting with 1-5% ether in hexane to give 1-[(4-methoxyphenyl)methyl]cyclopentanecarboxylic acid ethyl ester (80.8 g, 79%) as an oil.

Provenance & Evidence