Hydrochloric Acid → Benzoic acid, 4-(3-hydroxypropyl)-

Participants

Reaction Steps

To a chilled and stirred solution of diisopropylamine (4.63 ml, 33 mmole) in 20 ml of dry tetrahydrofuran at -78° C. (dry ice-acetone bath) under nitrogen was added dropwise 1.7M n-butyllithium in hexane (19.4 ml, 33 mmole). After 20 minutes, a solution of p-toluic acid (2.042 g, 15 mmole) in 20 ml of dry tetrahydrofuran was added dropwise. After strirring at -78° for another 1.5 hours, HMPA (4 ml) was added and then immediately followed by a solution of dry ethylene oxide (2.99 g, 67.9 mmole) in 10 ml of dry tetrahydrofuran. The resulting solution was stirred at -78° for two hours, acidified with 5% hydrochloric acid, warmed up to room temperature and most of the tetrahydrofuran removed in vacuo. The aqueous solution was saturated with sodium chloride and extracted with ethyl ether (3×100 ml). The combined ether extracts were concentrated to 100 ml and extracted with 0.5N sodium hydroxide solution (2×50 ml). This was acidified with 10% hydrochloric acid and extracted with ethyl ether (3×100 ml). The ether extracts were dried over anhydrous MgSO4 and evaporated in vacuo to give a gum. This was chromatographed on a silica gel (120 g, Baker 60-200 mesh) column, eluting successively with dichloromethane-ethyl acetate (9:1 and 1:1), ethyl acetate and dichloromethane-methanol (9:1) to give 750 mg (27.7% solid) of tlc-homogeneous title acid compound with a consistent H1 -NMR spectrum.

Provenance & Evidence