Azobisisobutyronitrile → 6-(Bromomethyl)pyridine-3-carbonitrile

Temperature

80 °C

Dissolve 6-methyl-nicotinonitrile (2 g, 17 mmol) and NBS (3.01 g, 17 mmol) in anhydrous DCE (56 mL) under nitrogen. Add AIBN (277 mg, 1.7 mmol) and heat the mixture at 80° C. for 1.5-2 h. Add another batch of AIBN (277 mg, 1.7 mmol) and heat the mixture at 80° C. for a further 1-2 h. Then add a third batch of AIBN (277 mg, 1.7 mmol) and heat the mixture at 80° C. for a further 1-2 h. Cool the reaction to room temperature and concentrate in vacuo. Dissolve the residue in DCM, add silica gel and concentrate in vacuo. Purify by chromatography on silica gel (120 g, pre-packed cartridge) eluting with cyclohexane/EtOAc (98:2 to 7:3 gradient over 55 min, 40 mL/min) to isolate the desired intermediate (2 g, 60%) as a white solid that turns red on standing at room temperature. MS (ES+) m/z: 199 (M+2)+.

1. temperatureheat the mixture at 80° C. for a further 1-2 h
2. temperatureCool
3. customthe reaction to room temperature
4. concentrationconcentrate in vacuo
5. dissolutionDissolve the residue in DCM
6. additionadd silica gel
7. concentrationconcentrate in vacuo
8. customPurify by chromatography on silica gel (120 g, pre-packed cartridge)
9. washeluting with cyclohexane/EtOAc (98:2 to 7:3 gradient over 55 min, 40 mL/min)

ORD record

ord-0537f77c7459497a8a31c829efa5b940

Source dataset

uspto-grants-2014_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08680091B2