Hydroxyphenylacetic acid → 3-(3,5-Dimethoxyphenyl)-2-(4-hydroxyphenyl)-acrylic acid

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3,5-dimethoxybenzaldehyde, 5, (500 g, 3.0 mol) and 4-hydroxyphenyl acetic acid, 6, (457 g, 3.0 mol) was added acetic anhydride (1.0 L, 10.60 mole) and triethylamine (420 mL, 3.0 mol). After stirring at 130-140° C. for 6 h, the mixture was cooled to room temperature. Concentrated HCl (1 L) was added to the reaction mixture slowly over 50 min while keeping the temperature between 20-30° C. The light yellow precipitate obtained was filtered and washed with water. The solid was dissolved in 3N NaOH (5 L) and stirred for 1 h and filtered. The filtrate was acidified to pH 1 with concentrated HCl while maintaining a temperature at 25-30° C. The precipitated product was filtered and washed with water to give crude product that was recrystallized from MeOH—H2O and dried at 40° C. for 6 h to yield 7 (428 g, 47%): mp 225-227° C. (lit. 226-228° C.)17; 1HNMR (360 MHz, DMSO-d6) δ12.48 (br s, 1H), 9.42 (s, 1H), 7.59 (s, 1H), 6.95 (d, J=8.0 Hz, 2H), 6.76 (d, J=8.0 Hz, 2H), 6.35 (t, J=2.2 Hz, 1H), 6.27 (d, J=2.2 Hz, 2H), 3.56 (s, 6H); MS (EI) m/z 299[M]−.

Provenance & Evidence