Hydrochloric Acid → 4-Cyclohexylmethyloxy-2-benzyl-benzoic acid

Participants

Reaction Conditions

Reaction Steps

A solution of 4-cyclohexylmethyloxybenzoic acid (19-1) (1.00 g, 4.27 mmol, 1 equiv) in tetrahydrofuran (10 mL) was added to a solution of sec-butyllithium (1.3M, 8.21 mL, 10.7 mmol, 2. 50 equiv) and N, N, N', N'-tetramethylethylenediamine (1.61 mL, 10.7 mmol, 2.50 equiv) in tetrahydrofuran (10 mL) at -100 ° C. (ethanol-N2 (l)). The resultant orange suspension was stirred at -100° C. for 1 h, then warmed to -78 ° C. and held at that temperature for 15 min. Benzyl bromide (2.00 mL, 16.8 mmol, 3.93 equiv) was added to the cold reaction mixture, causing the color to change to light yellow. The suspension was stirred at -78° C. for 35 min, then was poured into water (150 mL). The aqueous mixture was acidified to approximately pH 2 with an aqueous 1N hydrochloric acid solution and was extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over magnesium sulfate and were concentrated. The residue was purified by flash column chromatography (40% hexanes in ethyl acetate initially, grading to 100% ethyl acetate) to afford the desired carboxylic acid 19-2 as a white solid.

Provenance & Evidence