o-Anisalacetone → 5-(2-Methoxyphenyl)-1,3-cyclohexanedione

To a stirred solution of NaOEt (21% in EtOH) (9.8 ml, 26.5 mmol) under nitrogen was added diethylmalonate (3.7 ml, 24.3 mmol). The reaction mixture was stirred at ambient temperature for 20 min. 4-(2-methoxy-phenyl)-but-3-en-2-one (3.89 g, 22.1 mmol), Stage 1, was dissolved in ethanol (20 ml) and added to the reaction mixture, which was stirred at reflux and monitored by LC-MS until 4-(2-methoxy-phenyl)-but-3-en-2-one was consumed. The reaction mixture was cooled to ambient temperature. An aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which was heated at 80° C. for 1.5 h. Excess ethanol was removed by evaporation and the aqueous phase was washed with toluene (20 ml). The aqueous phase was acidified with conc. HCl (5 ml) and the reaction mixture was refluxed for 1 h and left to cool to ambient temperature. The compound was extracted with ethyl acetate (2×30 ml), dried with MgSO4 and filtered. The solvent was removed under reduced pressure. The title compound was purified by column chromatography eluting with ethyl acetate/heptane (1/1) to give a beige solid.

1. additionadded to the reaction mixture, which
2. stirringwas stirred
3. temperatureat reflux
4. customwas consumed
5. temperatureThe reaction mixture was cooled to ambient temperature
6. additionAn aqueous solution of sodium hydroxide (2M, 10 ml) was added to the reaction mixture, which
7. temperaturewas heated at 80° C. for 1.5 h
8. customExcess ethanol was removed by evaporation
9. washthe aqueous phase was washed with toluene (20 ml)
10. temperaturethe reaction mixture was refluxed for 1 h
11. waitleft
12. temperatureto cool to ambient temperature
13. extractionThe compound was extracted with ethyl acetate (2×30 ml)
14. dry with materialdried with MgSO4
15. filtrationfiltered
16. customThe solvent was removed under reduced pressure
17. customThe title compound was purified by column chromatography
18. washeluting with ethyl acetate/heptane (1/1)
19. customto give a beige solid

ORD record

ord-95435edea796485facc7ce4a3063a844

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592430B2