Dimethyl malonate → 5-(2-Bromo-4-fluorophenyl)-3-hydroxycyclohex-2-enone

Participants

Reaction Steps

To a 500 mL recovery flask was added (E)-4-(2-bromo-4-fluorophenyl)but-3-en-2-one (1B, 11.9 g, 49.0 mmol, 1.0 eq.) and MeOH (200 mL). Dimethyl malonate (1C, 6.47 g, 49.0 mmol, 1.0 eq.) was added, followed by NaOMe (30% wt in MeOH, 9.6 mL, 51.4 mmol, 1.05 eq.). The reaction mixture was refluxed overnight upon which it was concentrated to a brownish-red solid. The residue was taken up in 1N NaOH (150 mL) and refluxed for 1 h, during which the reaction color proceeded from cloudy-brown, to clear brown, to clear solution with brown precipitate. Concentrated HCl was carefully added until the mixture was acidic by pH paper. The reaction mixture was diluted with EtOAc (200 mL) and washed with saturated aqueous NaCl. The aqueous phase was extracted with EtOAc (lx 75 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated to give a foamy orange solid that was carried on to the next step without further purification (14.3 g, 100%). ESI-MS: m/z 285.2 (M+H)+.

Provenance & Evidence