6-Methylquinoline → (Quinolin-6-yl)acetonitrile

A solution of 6-methyl-quinoline (3.00 g, 20.6 mmol), N-bromosuccinimide (3.96 g, 22.0 mmol), and benzoyl peroxide (0.51 g, 2.10 mmol) in carbon tetrachloride (100 mL) is stirred at reflux for 2 h. The reaction is cooled to room temperature then washed with saturated aqueous sodium bisulfite (50 mL). The organic phase is passed through 30 g SiO2 (2×) eluting with dichloromethane then diethyl ether. N,N-Dimethylformamide (83 mL) is added to the combined organic fractions and solvent removed under reduced pressure leaving only the reaction mixture in N,N-dimethylformamide. To the reaction mixture in N,N-dimethylformamide is added sodium cyanide (1.22 g, 24.9 mmol) and potassium bicarbonate (2.51 g, 24.9 mmol). The reaction mixture is allowed to stir at 50° C. for 2 h. The cooled reaction mixture is poured into pH 7 buffer (75 mL) and extracted with ethyl acetate (2×100 mL). The organic layers are combined, washed with saturated aqueous sodium chloride (100 mL), dried over solid sodium chloride, and concentrated under reduced pressure to afford an oil that is purified by normal phase flash chromatography (120 g Biotage KP-Sil 40L: 10% ethyl acetate in hexanes for 5 min, 20% ethyl acetate in hexanes for 20 min, 40% ethyl acetate in hexanes for 20 min, 60% ethyl acetate in hexanes for 20 min, then 60-100% ethyl acetate in hexanes ramp over 20 min) to provids 645 mg (18%) of the title compound. MS ES+ m/e 169 (M+1).

1. temperatureat reflux for 2 h
2. washthen washed with saturated aqueous sodium bisulfite (50 mL)
3. washeluting with dichloromethane
4. additionN,N-Dimethylformamide (83 mL) is added to the combined organic fractions and solvent
5. customremoved under reduced pressure
6. customleaving only the reaction mixture in N,N-dimethylformamide
7. customThe cooled reaction mixture
8. additionis poured into pH 7 buffer (75 mL)
9. extractionextracted with ethyl acetate (2×100 mL)
10. washwashed with saturated aqueous sodium chloride (100 mL)
11. dry with materialdried over solid sodium chloride
12. concentrationconcentrated under reduced pressure
13. customto afford an oil that
14. customis purified by normal phase flash chromatography (120 g Biotage KP-Sil 40L
15. wait10% ethyl acetate in hexanes for 5 min
16. wait20% ethyl acetate in hexanes for 20 min
17. wait40% ethyl acetate in hexanes for 20 min
18. wait60% ethyl acetate in hexanes for 20 min
19. wait60-100% ethyl acetate in hexanes ramp over 20 min

ORD record

ord-0ddafcaa7a4c4934a5f45f40641eb3de

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07087626B2