Chloromethyl Methyl Ether → HCID 21707542, compound

To a reaction mixture containing 2,4-difluorophenol (25, 2 g, 15.37 mmol) in 30 mL of dry pyridine was added powdered KOH (0.854 g, 15.25 mmol) and methoxymethyl chloride (1.6 g, 19.37 mmol) and this reaction mixture was heated under reflux for 3.5 hours (FIG. 2E). The reaction was cooled and partitioned between 1 M NaOH and ethyl ether (2×30 mL). The organic solution was washed with 1 M HCl (2×20 mL), water, and then dried (MgSO4), filtered, and the solvent removed under vacuo to afford a oily residue. The crude product was purified by column chromatography (EtOAc:hexanes; 5:95) to afford the desired product as a pale yellow oil in 71% yield. 1H NMR (CDCl3) δ7.1-7.16 (m, 1 H, ArH), 6.78-6.88 (m, 2 H, ArH), 5.15 (s, 2 H, CH2), 3.52 (s, 3 H, CH3).

1. temperaturethis reaction mixture was heated
2. temperatureunder reflux for 3.5 hours (FIG. 2E)
3. temperatureThe reaction was cooled
4. custompartitioned between 1 M NaOH and ethyl ether (2×30 mL)
5. washThe organic solution was washed with 1 M HCl (2×20 mL), water
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customthe solvent removed under vacuo
9. customto afford a oily residue
10. customThe crude product was purified by column chromatography (EtOAc:hexanes; 5:95)

ORD record

ord-fbf1494af3dc47fe82a8576b2193b44e

Source dataset

uspto-grants-2001_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06284918B1