Isoamyl Nitrite → 4-Bromo-1-(methylthio)-2-(trifluoromethyl)-benzene

Temperature

25 °C

A solution of isoamyl nitrite (4.02 mL, 30 mmol) in dimethyl disulfide (19.8 mL, 220 mmol) at 25° C. was slowly treated with 4-bromo-2-(trifluoromethyl)aniline (4.8 g, 20 mmol). The reaction was exothermic with gas evolution. The resulting brown reaction mixture was heated to 80–90° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture indicated the absence of starting material. The reaction mixture was cooled to 25° C. and then concentrated in vacuo. The resulting residue was dissolved in ethyl acetate (200 mL). The organic layer was washed successively with a 1N aqueous hydrochloric acid solution (1×200 mL) and a saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 8/1 hexanes/ethyl acetate) afforded 4-bromo-1-methylsulfanyl-2-trifluoromethyl-benzene (4.73 g, 87%) as a brown oil: EI-HRMS m/e calcd for C8H6BrF3S (M+) 269.9326, found 269.9327.

1. temperatureThe resulting brown reaction mixture was heated to 80–90° C. for 2 h, at which time, thin layer chromatography analysis of the reaction mixture
2. concentrationconcentrated in vacuo
3. dissolutionThe resulting residue was dissolved in ethyl acetate (200 mL)
4. washThe organic layer was washed successively with a 1N aqueous hydrochloric acid solution (1×200 mL)
5. dry with materiala saturated aqueous sodium chloride solution (1×200 mL), dried over anhydrous magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo

ORD record

ord-728b160f6c8d4c1b9f1bc29fa5387081

Source dataset

uspto-grants-2007_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07223868B2