Hydrochloric Acid → 1-Bromo-2-fluoro-4-(methylsulfanyl)benzene

A stirred suspension of 1-bromo-2-fluoro-4-iodobenzene (100 g, 332 mmol), NiBr2 (7.26 g, 33.2 mmol), 2,2-dipyridyl (5.19 g, 33.2 mmol) and zinc dust (27.2 g, 415 mmol) in DMF (600 mL) was treated with MeS—SMe (15.65 g, 166 mmol), and the mixture was heated in a sand bath set for 80° C. After 10 min (color changes to black and reaction was complete according to HPLC analysis), the mixture was poured onto water. 1N HCl (100 mL) was added along with Et2O (300 mL), and the suspension was filtered through a glass fritted funnel. The zinc plug was further washed with Et2O and the Et2O layer was separated and the aqueous layer was extracted with Et2O (3×). The organic extracts were then dried over Na2SO4 and the solvent evaporated (note that the product is very volatile) to afford 1-bromo-2-fluoro-4-(methylthio)benzene (180 g), which was used without further purification. 1H NMR (400 MHz, CDCl3): δ 7.43-7.38 (m, 1H), 6.97 (dd, 1H, Ja=9.1 Hz, Jb=2.0 Hz), 6.90-6.86 (m, 1H), 2.46 (s, 3H).

1. temperaturethe mixture was heated in a sand bath
2. customset for 80° C
3. customAfter 10 min (color changes to black and reaction was complete according to HPLC analysis)
4. additionthe mixture was poured onto water
5. filtrationthe suspension was filtered through a glass fritted funnel
6. washThe zinc plug was further washed with Et2O
7. customthe Et2O layer was separated
8. extractionthe aqueous layer was extracted with Et2O (3×)
9. dry with materialThe organic extracts were then dried over Na2SO4
10. customthe solvent evaporated (note that the product

ORD-Eintrag

ord-2fb0a89bd610470ab9ef9c96608434fb

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08101634B2