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

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 (1×75 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)+.

1. temperatureThe reaction mixture was refluxed overnight upon which it
2. concentrationwas concentrated to a brownish-red solid
3. temperaturerefluxed for 1 h, during which the reaction color
4. additionConcentrated HCl was carefully added until the mixture
5. additionThe reaction mixture was diluted with EtOAc (200 mL)
6. washwashed with saturated aqueous NaCl
7. extractionThe aqueous phase was extracted with EtOAc (1×75 mL)
8. dry with materialThe organic phase was dried over anhydrous Na2SO4
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a foamy orange solid
12. customthat was carried on to the next step without further purification (14.3 g, 100%)

ORD record

ord-9e6ba334f3f14defa573eeab551670b8

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071766B2