Dimethylformamide → 3-(Trifluoromethyl)pyridine-2-carbonitrile

Temperature

120 °C

DMF (3500 mL), H2O (35 mL), 2-chloro-3-trifluoromethyl-pyridine (250 g; 1.38 mol), Zn(CN)2 (97 g; 0.83 mol), Pd2(dba)3 (19.0 g) and DPPF (22.4 g) are combined in a 22.0 liter flask. The reaction mixture is degassed by bubbling N2 into the reaction mixture over a period of 30 minutes. The reaction mixture is then heated to 120° C. for 4.5 hours, at which time an additional 9.5 g of Pd2(dba)3 and 11.2 g of DPPF is added to the reaction mixture. The reaction mixture is then heated at 120° C. for another 2 hours, and then allowed to cool to room temperature overnight. The resulting dark brown solution is cooled in ice and cold water. A mixture of saturated NH4Cl (1380 mL), 28%NH4OH (345 mL and water (1380 mL) is then added and the mixture is stirred in an ice bath for 1 hour. To this stirred mixture is added 3.0 liters of EtOAc, and the mixture is stirred for 15 minutes. The EtOAc layer is separated from the mixture by suction the extraction is repeated another four times with EtOAc (2×2 liters, 2×1.5 liters). The combined EtOAc extracts are filtered through one inch of celite and dried with Na2SO4 (500 g). The dried extract is filtered and concentrated in vacuum at 40° C. initially to a volume of three liters. The mixture is concentrated at 80° C. under vacuum to afford a dark brown oil, which is distilled under vacuum to give 2-cyano-3-trifluoromethylpyridine.

1. customThe reaction mixture is degassed
2. customby bubbling N2 into the reaction mixture over a period of 30 minutes
3. additionis added to the reaction mixture
4. temperatureThe reaction mixture is then heated at 120° C. for another 2 hours
5. temperatureto cool to room temperature overnight
6. temperatureThe resulting dark brown solution is cooled in ice
7. additionA mixture of saturated NH4Cl (1380 mL), 28%NH4OH (345 mL and water (1380 mL)
8. additionis then added
9. additionTo this stirred mixture is added 3.0 liters of EtOAc
10. stirringthe mixture is stirred for 15 minutes
11. customThe EtOAc layer is separated from the mixture by suction
12. extractionthe extraction
13. filtrationThe combined EtOAc extracts are filtered through one inch of celite
14. dry with materialdried with Na2SO4 (500 g)
15. extractionThe dried extract
16. filtrationis filtered
17. concentrationconcentrated in vacuum at 40° C. initially to a volume of three liters
18. concentrationThe mixture is concentrated at 80° C. under vacuum
19. customto afford a dark brown oil, which
20. distillationis distilled under vacuum

ORD record

ord-20d3af4d67684140b9d47c4633fb062f

Source dataset

uspto-grants-2009_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07488740B2