Acetic Acid → Racemic methyl 2-(3,4-dichlorophenyl)-4-oxochroman-3-carboxylate

Participants

Reaction Steps

A mixture of methyl 3-(2-hydroxyphenyl)-3-oxopropanoate (prepared according to Cushman, M. et al., J. Med. Chem. 1991, 34, 798; 500 mg, 2.56 mmol) and 3,4-dichlorobenzaldehyde (496 mg, 2.83 mmol) in isopropanol (5.0 mL) was treated with piperidine (25 μl, 257 μmol) and acetic acid (15 μl, 257 μmol) and then heated to reflux for 20 h. At the conclusion of this period, the mixture was cooled on ice, causing a gum to separate from the solution. The mixture was treated with a small amount of water and heated until homogeneous. On slow cooling to rt, a solid formed, which was collected by filtration and dried under vacuum to provide racemic methyl 2-(3,4-dichlorophenyl)-4-oxochroman-3-carboxylate as an off-white powder (496 mg, 55%). An additional sample (57 mg, 6%) was obtained by partial concentration of the filtrate. The NMR indicated predominantly the enolic form. 1H NMR (400 MHz, CDCl3) δ ppm 3.78 (s, 3 H) 6.18 (s, 1 H) 6.81 (dd, J=8.1, 1.0 Hz, 1H) 6.99 (td, J=7.4, 1.0 Hz, 1 H) 7.19 (dd, J=8.4, 1.8 Hz, 1 H) 7.31 (m, 1 H) 7.34 (d, J=8.1 Hz, 1 H) 7.43 (d, J=2.0 Hz, 1 H) 7.69 (dd, J=7.9, 1.8 Hz, 1 H) 12.28 (br. s, 1H). High resolution mass spectrum m/z found 373.0016, calcd 373.0010 (M+Na)+.

Provenance & Evidence