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

Dissolve 2-chloro-3-trifluoromethylpyridine (36.2 g, 0.2 moles) in DMF (350 mL) at room temperature. Add water (3.5 mL) and zinc cyanide (14 g, 0.12 moles) to the reaction mixture and degas with nitrogen for 15 minutes. Add catalyst Pd2(dba)3 (5.5 g, 3 mol %) and ligand DPPF (6.5 g, 6 mol %) to the mixture and then heat at 120° C. with stirring for 1 hour. Cool the reaction mixture in an ice bath and then add saturated ammonium chloride (200 mL), 28% ammonium hydroxide (50 mL) and water (50 mL). Stir the resulting reaction mixture in the ice bath for 1 hour and then dilute it EtOAc (300 mL). Separate the organic layer, extract the aqueous layer with EtOAc (3×300 mL), wash the combined organic layers with brine (2×200 mL) and dry (MgSO4). Filter the dried extract and concentrate under vacuum to afford crude product as dark brown oil. Purify the crude product by vacuum distillation to afford pure product as colorless oil.

1. temperatureCool the reaction mixture in an ice bath
2. stirringStir
3. customSeparate the organic layer
4. extractionextract the aqueous layer with EtOAc (3×300 mL)
5. washwash the combined organic layers with brine (2×200 mL)
6. dry with materialdry (MgSO4)
7. filtrationFilter the dried
8. extractionextract
9. concentrationconcentrate under vacuum
10. customto afford crude product as dark brown oil
11. customPurify the crude product
12. distillationby vacuum distillation
13. customto afford pure product as colorless oil

ORD record

ord-ef8d7a64e6e24f98b855605f2cf2c94e

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07329664B2