Sodium Cyanide → 3-Pyridineacetonitrile, 6-(trifluoromethyl)-

Temperature

0 °C

To a solution of (6-trifluoromethyl-pyridin-3-yl)-methanol (4.93 g, 27.8 mmol) in THF (50 mL) were added N,N-diisopropyl ethyl amine (5.7 mL, 33 mmol) and 4-dimethylaminopyridine (17 mg, 0.14 mmol). After cooling to 0° C. thionyl chloride (4.8 mL, 56 mmol) was added dropwise over a period of 10 min. After stirring for 30 min. at 0° C., the ice bath was replaced with a water bath and stirred for 2 h at ambient temperature. The resulting brown reaction mixture was concentrated in vacuo, diluted with TBME (50 mL) and cooled to 0° C. before aqueous NaHCO3 (1M, 100 mL) was added. The mixture was stirred for 30 min., the aqueous layers were extracted with TBME (50 mL) and the combined organic layers were washed with aqueous NaHCO3 (1M, 50 mL) and brine (50 mL). Drying over sodium sulphate was followed by concentration. The resulting oil (6.44 g) was dissolved in DMSO (15 mL) and sodium cyanide (1.36 g, 27.8 mmol) was added. The resulting dark reaction mixture was stirred for 18 h at ambient temperature under a nitrogen atmosphere. It was diluted with TBME (50 mL) and treated with ice (30 g) and water (50 mL). The aqueous layer was separated and extracted with TBME (50 mL). The organic layers were washed twice with water (50 mL) and brine (30 mL), dried over sodium sulfate and concentrated. Purification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 50:50) afforded the title compound (3.59 g, 59%) as a light brown oil. MS m/e: 185.3 [M−H]−.

1. additionwas added dropwise over a period of 10 min
2. stirringstirred for 2 h at ambient temperature
3. concentrationThe resulting brown reaction mixture was concentrated in vacuo
4. additiondiluted with TBME (50 mL)
5. temperaturecooled to 0° C. before aqueous NaHCO3 (1M, 100 mL)
6. additionwas added
7. stirringThe mixture was stirred for 30 min.
8. extractionthe aqueous layers were extracted with TBME (50 mL)
9. washthe combined organic layers were washed with aqueous NaHCO3 (1M, 50 mL) and brine (50 mL)
10. dry with materialDrying over sodium sulphate
11. concentrationwas followed by concentration
12. dissolutionThe resulting oil (6.44 g) was dissolved in DMSO (15 mL)
13. customThe resulting dark reaction mixture
14. stirringwas stirred for 18 h at ambient temperature under a nitrogen atmosphere
15. customThe aqueous layer was separated
16. extractionextracted with TBME (50 mL)
17. washThe organic layers were washed twice with water (50 mL) and brine (30 mL)
18. dry with materialdried over sodium sulfate
19. concentrationconcentrated
20. customPurification by chromatography (SiO2, heptane:ethyl acetate=95:5 to 50:50)

ORD record

ord-67a146b849ce40da87653dc8c50c6d07

Source dataset

uspto-grants-2012_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08133909B2