Acetonitrile → 3-Hydroxy-3-(pyridin-4-yl)propanenitrile

Temperature

0 °C

Diisopropylamine (1.98 g, 19.6 mmol) was added dropwise to a solution of a butyllithium/hexane solution (10.5 ml, 16.8 mmol) in anhydrous tetrahydrofuran (20 ml) at −80° C. over five minutes, the temperature was raised to 0° C., and the mixture was stirred for 30 minutes. The mixture was cooled to −80° C. again, then acetonitrile (573 mg, 14.0 mmol) was added dropwise to the mixture over seven minutes, and after 20 minutes, 4-pyridinecarboxyaldehyde (758 mg, 7.08 mmol) was added dropwise thereto over 10 minutes. After 50 minutes, a saturated aqueous ammonium chloride solution (20 ml) was added to the reaction mixture, and the temperature was raised to room temperature. The whole was continuously extracted (ethyl acetate and water) for four days. The organic layer was dried over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give 3-hydroxy-3-(4-pyridyl)propionitrile (666 mg, colorless crystals, 63.5%).

1. temperatureThe mixture was cooled to −80° C. again
2. waitafter 20 minutes
3. addition4-pyridinecarboxyaldehyde (758 mg, 7.08 mmol) was added dropwise
4. waitover 10 minutes
5. waitAfter 50 minutes
6. temperaturethe temperature was raised to room temperature
7. extractionThe whole was continuously extracted (ethyl acetate and water) for four days
8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
9. customthe solvent was evaporated under reduced pressure
10. customthe residue was purified by silica gel column chromatography

ORD record

ord-c7b3add2a6ae4a98b5d953ced399dcab

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07345064B2