4-Bromophenol → 1-Bromo-4-(methoxymethoxy)benzene

Add sodium hydride (2.78 g of 95% dry, 0.116 mol) in portions to a 500 mL three-necked flask equipped with a nitrogen inlet, magnetic stir bar and DMF (200 mL) at −10 to −15° C. Add a solution of 4-bromophenol (20.00 g, 0.116 mol) in DMF (100 mL) over about 20 minutes, maintaining the internal temperature of the reaction below −5° C. Stir the reaction for 1 hour and then add MOMCl (8.81 mL, 0.116 mol) in portions to maintain the internal temperature below −5° C. Stir the mixture for 3 hours and then add ice until gas evolution ceases. Pour the reaction into ice-H2O (500 mL) and extract with EtOAc (2×300 mL). Wash the combined organic extracts with 1 N NaOH (500 mL), H2O (500 mL) and brine (400 mL). Dry the solution (MgSO4), filter and concentrate to obtain the title product (23.94 g, 93%) as an oil which may be used without further purification. 1H NMR (CDCl3) δ 3.46 (s, 3H), 5.14 (s, 2H), 6.92 (d, J =9.0 Hz, 2H), 7.37 (d, J=9.0 Hz, 2H).

1. customequipped with a nitrogen inlet, magnetic stir bar
2. customat −10 to −15° C
3. temperaturemaintaining
4. customthe internal temperature of the reaction below −5° C
5. customthe reaction for 1 hour
6. stirringStir the mixture for 3 hours
7. additionPour
8. extractionextract with EtOAc (2×300 mL)
9. washWash the combined organic extracts with 1 N NaOH (500 mL), H2O (500 mL) and brine (400 mL)
10. dry with materialDry the solution (MgSO4)
11. filtrationfilter
12. concentrationconcentrate

ORD record

ord-a51fb56293084904b654586e389fd81e

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07279499B2