Hydrochloric Acid → 3-Cyclopentyl-2-(4-phenoxy-phenyl)propionic acid

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (2.52 mL, 19.3 mmol) in tetrahydrofuran (50 mL) was cooled to −78° C. under a nitrogen atmosphere and then treated with a 2.5M solution of n-butyllithium in hexanes (7.7 mL, 19.3 mmol). The reaction mixture was stirred at −78° C. for 15 min and then slowly treated with a solution of 4-phenoxyphenylacetic acid (2.00 g, 8.8 mmol) in tetrahydrofuran (12 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (4 mL) via cannulation. The resulting bright yellow solution was allowed to stir for 1 h at −78° C. After this time, the reaction mixture was treated with a solution of iodomethylcyclopentane (2.02 g, 9.6 mmol) in 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (1 mL) via cannulation. The resulting reaction mixture was stirred for 1 h at −78° C. and then allowed to warm to 25° C. where it was stirred for 14 h. The reaction was then acidified to pH=2 by the dropwise addition of a 1N aqueous hydrochloric acid solution and then extracted with ethyl acetate (3×25 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 50/50 hexanes/ethyl acetate plus 1% acetic acid) afforded 3-cyclopentyl-2-(4-phenoxy-phenyl)propionic acid (2.49 g, 91%) as a white foam: EI-HRMS m/e calcd for C20H22O3 (M+) 310.1568, found 310.1568.

Provenance & Evidence