Azobisisobutyronitrile → 2-(2-Bromo-6-fluorophenyl)acetonitrile

A suspension of 2-bromo-6-fluorotoluene (5.00 g, 26.45 mmol), NBS (5.18 g, 29.10 mmol), and VAZO (323 mg, 1.32 mmol) in CCl4 (100 mL) was heated to reflux under vigoroue stirring overnight. The reaction mixture was cooled to room temperature, concentrated and the residue was removed by filtration. The filtrate was concentrated and the residue was re-dissolved in ethanol (90 mL), treated with a solution of NaCN (2.59 g, 52.9 mmol) in water (20 mL) and the combined mixture was heated to reflux for 5 hrs. Ethanol was removed under reduced pressure, the aqueous residue was diluted with water and extracted with AcOEt. The organic layer was successively washed with water and brine, concentrated, adsorbed on silica gel and purified by flash column chromatography (eluents AcOEt/hexanes: 10/90 to 20/80) to afford title compound 329 (3.92 g, 69% yield over 2 steps, slightly contaminated) as a pale yellow sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 7.62-7.57 (m, 1H), 7.45-7.35 (m, 2H), 4.08 (s, 2H).

1. temperaturewas heated
2. temperatureto reflux under vigoroue
3. concentrationconcentrated
4. customthe residue was removed by filtration
5. concentrationThe filtrate was concentrated
6. dissolutionthe residue was re-dissolved in ethanol (90 mL)
7. temperaturethe combined mixture was heated
8. temperatureto reflux for 5 hrs
9. customEthanol was removed under reduced pressure
10. additionthe aqueous residue was diluted with water
11. extractionextracted with AcOEt
12. washThe organic layer was successively washed with water and brine
13. concentrationconcentrated
14. custompurified by flash column chromatography (eluents AcOEt/hexanes: 10/90 to 20/80)

ORD record

ord-7aba173249d141a3bdf6e8509eb575d4

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07790729B2