Acetic Acid → HCID 67054849, compound

A solution of 1-(2-fluoro-4-hydroxy-5-methoxyphenyl)ethanone (18.0 g; 97.7 mmol; 1 eq; which may be prepared as hereinbefore described for D1) in glacial acetic acid (800 mL) is stirred at 70° C. before adding added zinc dust (63.9 g; 977 mmol; 10 eq). The resulting grey heterogeneous mixture is then heated at reflux and stirred overnight using a mechanical stirrer. After this period, zinc has aggregated and conversion rate reaches 90% according to the 1H NMR analysis of a crude aliquot. Therefore, the zinc metal is removed by filtration on a fritted glass and fresh zinc dust (6.4 g; 98 mmol) is added to the resulting limpid yellow filtrate. The solution is heated at reflux overnight until completion of the reaction. The solution is filtered on a fritted glass and basified until pH 11-12 is reached with a saturated aqueous solution of potassium carbonate (1.5 L) and with additional solid potassium carbonate if needed. The resulting aqueous layer is then extracted with ethyl acetate (1.0 L), dried over sodium sulphate or by azeotropic toluene distillation, filtered and concentrated under vacuum to afford the pure title compound (16.1 g; 94.7 mmol; 97%) as a pale yellow oil. It should be noted that the title compound is a volatile product and should be kept in the fridge under Argon away from light (darkens with oxygen and/or UV exposure).

1. additionbefore adding
2. temperatureThe resulting grey heterogeneous mixture is then heated
3. temperatureat reflux
4. waitAfter this period
5. additionis added to the resulting limpid yellow filtrate
6. temperatureThe solution is heated
7. temperatureat reflux overnight until completion of the reaction
8. filtrationThe solution is filtered on a fritted glass
9. extractionThe resulting aqueous layer is then extracted with ethyl acetate (1.0 L)
10. dry with materialdried over sodium sulphate or by azeotropic toluene distillation
11. filtrationfiltered
12. concentrationconcentrated under vacuum

ORD record

ord-92d559c67766434e914635cf6907269a

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09272985B2