Water → 4-(Piperidin-4-yloxy)benzonitrile

A solution of 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (14.99 g) and 4-chlorobenzonitrile (10.35 g) in DMF (100 mL) was treated with sodium hydride (60%, 3.8 g). The resulting dark mixture was then heated to 65 C for 16 h, and allowed to cool to RT. The mixture was poured into water (1 L) and extracted with ether (3×400 mL). The combined organic phases were evaporated and the brown oil dissolved in methanol (500 mL) and treated with concentrated hydrochloric acid (20 mL). After 24 h the methanol was removed, 5% aqueous sodium hydroxide (300 mL) and water (300 mL) were added, and the mixture was extracted with DCM (3×300 mL). The combined organic phases were dried (sodium sulfate) and evaporated. Bulb to bulb distillation of the residue gave the title compound as an off white waxy solid (12.23 g).

1. temperatureThe resulting dark mixture was then heated to 65 C for 16 h
2. extractionextracted with ether (3×400 mL)
3. customThe combined organic phases were evaporated
4. dissolutionthe brown oil dissolved in methanol (500 mL)
5. additiontreated with concentrated hydrochloric acid (20 mL)
6. customAfter 24 h the methanol was removed
7. addition5% aqueous sodium hydroxide (300 mL) and water (300 mL) were added
8. extractionthe mixture was extracted with DCM (3×300 mL)
9. dry with materialThe combined organic phases were dried (sodium sulfate)
10. customevaporated
11. distillationBulb to bulb distillation of the residue

ORD record

ord-c480cce5b1354bee8575792901bce1a7

Source dataset

uspto-grants-2007_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07241778B2