Chloromethyl Methyl Ether → 4-Bromo-1-fluoro-2-(methoxymethoxy)benzene

To a stirred solution of 5-bromo-2-fluorophenol (5 g, 26.2 mmol) in DMF (50 mL) at 0° C. was added sodium hydride (1.571 g, 39.3 mmol). After stirring for 10 min, chloromethyl methyl ether (2.386 mL, 31.4 mmol) was added dropwise to mixture and the mixture was then stirred for 1 hour at 0° C. The reaction was quenched with addition of saturated NH4Cl aq. and the mixture was poured into water (150 mL). The mixture was extracted with ethyl acetate (30 mL×2). The organic layers were combined, washed with brine (100 mL), dried over MgSO4, filtered and evaporated in vacuo. The crude residue was purified by chromatography on silica, eluting with a gradient of 0-10% ethyl acetate in cyclohexane to give the title compound (5.90 g). 1H NMR (CDCl3, 400 MHz) δ ppm: 3.55 (3H, s), 5.24 (2H, s), 6.95-7.02 (1H, m), 7.08-7.14 (1H, m), 7.36-7.40 (1H, m).

1. stirringthe mixture was then stirred for 1 hour at 0° C
2. customThe reaction was quenched with addition of saturated NH4Cl aq.
3. additionthe mixture was poured into water (150 mL)
4. extractionThe mixture was extracted with ethyl acetate (30 mL×2)
5. washwashed with brine (100 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. customevaporated in vacuo
9. customThe crude residue was purified by chromatography on silica
10. washeluting with a gradient of 0-10% ethyl acetate in cyclohexane

ORD record

ord-1c7eb7f648964c12ae5294fb4e420c08

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08877742B2