Felbinac → 2-Biphenyl-4-yl-3-cyclopentylpropionic acid

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (6.93 mL, 49.5 mmol) in dry tetrahydrofuran (64 mL) and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone (16 mL) was cooled to −78° C. under nitrogen and then treated with a 2.5M solution of n-butyllithium in hexanes (19.8 mL, 49.5 mmol). The yellow reaction mixture was stirred at −78° C. for 30 min and then treated dropwise with a solution of 4-biphenylacetic acid (5.00 g, 23.6 mmol) in a small amount of dry tetrahydrofuran. The reaction mixture turned dark in color and was allowed to stir at −78° C. for 45 min, at which time, a solution of iodomethylcyclopentane (4.96 g, 23.6 mmol) in a small amount of dry tetrahydrofuran was added dropwise. The reaction mixture was allowed to warm to 25° C. over a period of 15 h. The reaction mixture was quenched with water (100 mL), and the reaction mixture was concentrated in vacuo to remove tetrahydrofuran. The remaining aqueous layer was acidified to pH=2 with concentrated hydrochloric acid and then extracted with ethyl acetate (2×150 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 2-biphenyl-4-yl-3-cyclopentylpropionic acid (5.13 g, 74%) as a white solid: mp 131-133° C.; FAB-HRMS m/e calcd for C20H22O2 (M+H)+ 294.1620, found 294.1626.

Provenance & Evidence