Dimethyl Disulfide → 1-Bromo-4-chloro-3-methylthio-2-fluorobenzene

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. and a solution of dimethyldisulfide (18.8 g, 0.20 mol) in THF (50 mL) was slowly added and the mixture was warmed to ambient temperature. The reaction was quenched with water (200 mL) and extracted with ethyl acetate (2×150 mL) and the combined organic phases dried (sodium sulfate) and concentrated. The residual red oil was purified by chromatography (5% ethyl acetate in hexanes) to give 1-bromo-4-chloro-2-fluoro-3-(methylthio)benzene (23.9 g, 0.094 mol): 1H NMR (CDCl3): δ 7.40 (m, 1H), 7.15 (dd, 1H), 2.50 (s, 3H).

1. additionAfter addition
2. temperaturecooled to −50° C.
3. temperaturethe mixture was warmed to ambient temperature
4. customThe reaction was quenched with water (200 mL)
5. extractionextracted with ethyl acetate (2×150 mL)
6. dry with materialthe combined organic phases dried (sodium sulfate)
7. concentrationconcentrated
8. customThe residual red oil was purified by chromatography (5% ethyl acetate in hexanes)

ORD record

ord-955dd2f4770745cb8dcda679fed99e91

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07498468B2