Acetic Acid → 4-(4-Hydroxyphenyl)butanoic acid

Participants

Reaction Conditions

Reaction Steps

A 22-L 4-necked round bottom flask was equipped with a condenser, nitrogen inlet, thermometer lead and overhead stirring apparatus. The flask was charged with 4-(4-methoxyphenyl)butyric acid (2250 g, 11.58 moles) followed by pyridine hydrochloride (5360 g, 46.34 moles, 4 eq). The resulting mixture of the two solids was heated under nitrogen to 185-195° C., with stirring commencing by 50° C. The flask contents were held at 185-195° C., and reaction progress was monitored by TLC (50/50 v/v hexanes/ethyl acetate+1% v/v acetic acid, panisaldehyde stain for visualization). After two hours, TLC analysis indicated complete consumption of starting material. The heat source was removed and the mixture allowed to cool to 90° C., after which 5N HCl (2900 mL, 14.47 moles, 1.25 eq) and H2O (2700 mL) were added sequentially. Stirring was continued until the pot temperature reached 35° C. The mixture was transferred to a 22-L bottom-outlet flask and diluted with t-butyl methyl ether (MTBE, 6000 mL). The layers were separated and the aqueous portion was reextracted with MTBE (3×4000 mL). The organic portions were combined and back-washed with 5N HCl (750 mL). After drying (Na2SO4) and filtration, the solution was concentrated in vacuo to afford the title compound as a white solid (2020 g, 96.7%). 1H NMR (500 MHz, DMSO-d6) δ 1.70 (m, 2H), 2.15 (t, 2H), 2.45 (t, 2H), 3.33 (s, 1H), 6.65 (d, 2H), 6.95 (d, 2H). 13C NMR (DMSO-d6) δ 26.5, 32.5, 33.5, 114.6, 129.0, 131.2, 155.3, 174.2.

Provenance & Evidence