Acetonitrile → 3-(2-Chloro-phenyl)-3-hydroxy-butyronitrile

Temperature

-78 °C

To a stirring solution of diisopropylamine (0.97 mL, 6.83 mmol) in tetrahydrofuran (15 mL) at −78° C. under nitrogen was added a solution of n-butyllithium (2.86 mL, 7.14 mmol, 2.5 M in hexane). After the addition was complete, the mixture was stirred at −78° C. for 10 minutes and removed cooling bath for 5 minutes. The mixture was cooled back to −78° C., acetonitrile (0.33 mL, 6.21 mmol) was added and the reaction mixture was then stirred at −78° C. for 30 minutes. 1-(2-Chloro-phenyl)-ethanone (1 mL, 7.45 mmol) was added and the resulting solution was allowed to warm to ambient temperature. After 18 hours at ambient temperature, saturated aqueous ammonium chloride (5 mL) was added to the reaction mixture and it was concentrated at reduced pressure. The resulting crude product was diluted with ethyl acetate (30 mL), washed with water (15 mL) followed by saturated aqueous sodium chloride (10 mL). The organic layer was concentrated and purified by column chromatography (40 g silica gel cartridge) eluting with ethyl acetate/hexane (0%-15%) to give the product as a colorless oil (1.1 g, 90%).

1. additionAfter the addition
2. customremoved
3. temperaturecooling bath for 5 minutes
4. temperatureThe mixture was cooled back to −78° C.
5. stirringthe reaction mixture was then stirred at −78° C. for 30 minutes
6. temperatureto warm to ambient temperature
7. waitAfter 18 hours at ambient temperature
8. concentrationwas concentrated at reduced pressure
9. additionThe resulting crude product was diluted with ethyl acetate (30 mL)
10. washwashed with water (15 mL)
11. concentrationThe organic layer was concentrated
12. custompurified by column chromatography (40 g silica gel cartridge)
13. washeluting with ethyl acetate/hexane (0%-15%)

ORD record

ord-576eb4aa395b4726b6ba231f9f14bc96

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08609849B1