Ethylene Glycol → Methyl 2,5-difluoro-3-methoxyphenylacetate

Temperature

120 °C

To a stirred solution of 2,5-difluoro-3-methoxyphenylacetonitrile (5.92 g, 30 mmol) in ethylene glycol (150 ml) was added potassium hydroxide (85%; 3.0 g, 45 mmol). The mixture was heated at 120° C. for 1 hr and then the mixture was poured into water (100 ml) and washed with ether (100 ml). The aqueous layer was acidified with 6N HCl (10 ml) and extracted with ether (200 ml). The extract was washed with water (50 ml), brine (50 ml), dried (magnesium sulfate) and evaporated. The residual solid was dissolved in methanol (200 ml) and to the solution was added conc. sulfuric acid (2 ml). The resulting mixture was heated at reflux for 1 hr, cooled and concentrated in vacuo. The residue was dissolved in ether (100 ml), washed with water (100 ml), saturated aqueous sodium hydrogen carbonate (100 ml), brine (100 ml) and dried over magnesium sulfate. Removal of solvent gave 3.80 g (59%) of the titled compound as a yellow oil.

1. washwashed with ether (100 ml)
2. extractionextracted with ether (200 ml)
3. washThe extract was washed with water (50 ml), brine (50 ml)
4. dry with materialdried (magnesium sulfate)
5. customevaporated
6. dissolutionThe residual solid was dissolved in methanol (200 ml) and to the solution
7. additionwas added conc. sulfuric acid (2 ml)
8. temperatureThe resulting mixture was heated
9. temperatureat reflux for 1 hr
10. temperaturecooled
11. concentrationconcentrated in vacuo
12. dissolutionThe residue was dissolved in ether (100 ml)
13. washwashed with water (100 ml), saturated aqueous sodium hydrogen carbonate (100 ml), brine (100 ml)
14. dry with materialdried over magnesium sulfate
15. customRemoval of solvent

ORD record

ord-16a3bd03ebb742988a389ddeb0f1708f

Source dataset

uspto-grants-2000_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06063928