Acetic Acid → HCID 23195023, compound

Participants

Reaction Steps

A 1 liter 3 neck round-bottomed flask was charged with 35.7 g (150 mmols) of the 5-(2,4-dimethoxyphenyl)-pentanoic acid (4a) and a stir bar. The flask was set into a suitably sized heating mantle supported on a stirring plate with a strong stirring magnet. The flask was fitted with a thermometer, reflux condenser, and argon inlet. Then 400 ml of acetic acid was added via the thermometer port. The mixture was stirred and warmed to dissolve the solid. This was followed by addition of 68 ml (600 mmols) of 48% aqueous hydrobromic acid. The thermometer was replaced and the flask was flushed with argon. With the cooling water on, the flask was heated to reflux. The reflux was maintained for 16 hours, the mixture was cooled and concentrated on a rotary evaporator. 1 L of methanol was added, and HCl was bubbled in for 5 minutes with a sparger, at a moderate rate. The warm solution was allowed to cool and evaporated. The resulting syrup dissolved in 200 ml of ethyl acetate. The solution was washed with 100 ml water, twice with 100 ml of saturated sodium bicarbonate and once with saturated sodium chloride. The organic layer was dried over sodium sulfate and evaporated to a syrup. The crude product was purified on silica eluting with 3:1 to 2:1 hexane-ethyl acetate. Concentration of the pure product fractions afforded 18.5 g (55%) of desired product. 1H NMR (DMSO-d6) δ: 9.01 (s, 1H), 8.92 (s, 1H), 6.75 (d, J=8.2 Hz, 1H), 6.23 (d, J=2 Hz, 1H), 6.10 (dd, J1=2 Hz, J2=8.2 Hz, 1H), 3.56 (s, 3H), 2.37 (t, J=7 Hz, 2H), 2.29 (t, J=7 Hz, 2H), 1.48 (m, 4H).

Provenance & Evidence