Bromomethyl methyl ether → 1-Bromo-4-chloro-2-fluoro-3-(methoxymethyl)benzene

Temperature

-20 °C

A solution of 1-bromo-4-chloro-2-fluorobenzene (20.4 g, 0.100 mol) in THF (50 mL) was slowly added to LDA (0.125 mol) in THF (600 mL) at −50° C. After addition the solution was warmed to −20° C. and then cooled to −50° C. a solution of bromomethoxymethane (25 g, 0.200 mol) in THF (25 mL) was slowly added and the reaction mixture was warmed to ambient temperature. The reaction was quenched with water (400 mL) and extracted with diethyl ether (2×150 mL). The combined organic phases were dried (sodium sulfate) and concentrated. The residual oil was distilled (70°-75° C./0.5 mm) to give 1-bromo-4-chloro-2-fluoro-3-methoxymethylbenzene (18.0 g, 0.071 mol): 1H NMR (CDCl3): δ 7.50 (m, 1H), 7.15 (dd, 1H), 4.65 (s, 1H), 3.40 (s, 1H).

1. additionAfter addition the solution
2. additionwas slowly added
3. temperaturethe reaction mixture was warmed to ambient temperature
4. customThe reaction was quenched with water (400 mL)
5. extractionextracted with diethyl ether (2×150 mL)
6. dry with materialThe combined organic phases were dried (sodium sulfate)
7. concentrationconcentrated
8. distillationThe residual oil was distilled (70°-75° C./0.5 mm)

ORD record

ord-3a11670a4488410a9c3499f7a22e5f03

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07498468B2