Tetrabutylammonium Fluoride → 4-(4-Hydroxypiperidin-1-yl)benzonitrile

Tetra-n-butylammonium fluoride (1M) THF solution (10.6 ml, 10.2 mmol) was added to a mixture of 4-[4-(tert-butyldimethylsiloxy)piperidin-1-yl]benzonitrile (2.8 g, 8.85 mmol) prepared in Reference Example 28 in THF (30 ml) while cooling in an ice-bath, and the mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate twice. The extract was washed with water and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/2) to afford 4-(4-hydroxypiperidin-1-yl)benzonitrile (1.52 g, yield 85%) as a colorless crystalline powder.

1. temperaturewhile cooling in an ice-bath
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additionWater was added to the residue
4. extractionthe mixture was extracted with ethyl acetate twice
5. washThe extract was washed with water and brine
6. dry with materialdried over magnesium sulfate
7. filtrationAfter filtration
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=1/2)

ORD record

ord-c402e54a7cb64713acdfac4cd6776506

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2