4-Bromobutyronitrile → 4-{3-[(Piperidin-1-yl)methyl]phenoxy}butanenitrile

HRID 1382772Notes

Reaction equation

HRID 1382772 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:18][CH2:19][CH2:20][C:21]#[N:22]>O1CCCC1>[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH:11]=[CH:12][CH:13]=2)[O:14][CH2:18][CH2:19][CH2:20][C:21]#[N:22])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 214124-BromobutyronitrileHCID 24758Sodium hydrideHCID 8269741-(3-Hydroxybenzyl)piperidine

Product 1

HCID 197625514-{3-[(Piperidin-1-yl)methyl]phenoxy}butanenitrileYield 69.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 3-(1-piperidinylmethyl)phenol (12.05 g) in dry tetrahydrofuran (50 ml) was added dropwise to a suspension of sodium hydride [from 6.0 g of 50% suspension in oil washed with petroleum ether] in dry tetrahydrofuran (70 ml). The mixture was stirred under reflux for 30 minutes and allowed to cool. 4-Bromobutyronitrile (14.89 g, 10.0 ml) was added to the cool mixture and the mixture so obtained was stirred under reflux for 22 hours. Tetrahydrofuran was evaporated under reduced pressure and the residue was dissolved in water (100 ml). The solution was extracted with ether (3×50 ml), and the aqueous layer was adjusted to pH 9 with K2CO3. The aqueous solution was extracted with chloroform (3×100 ml), the chloroform extracts were dried (K2CO3 and chloroform was removed under reduced pressure to give a pale brown oil, (16.22 g). This oil was purified by column chromatography (Kieselgel 60 70-230 mesh silica) using chloroform as eluant. The fractions containing the desired product were collected and the solvent was evaporated in vacuo to give 4-[3-(1-piperidinylmethyl)phenoxy]butyronitrile as an oil (11.37 g).

Workup

  1. temperatureunder reflux for 30 minutes
  2. temperatureto cool
  3. customthe mixture so obtained
  4. stirringwas stirred
  5. temperatureunder reflux for 22 hours
  6. customTetrahydrofuran was evaporated under reduced pressure
  7. dissolutionthe residue was dissolved in water (100 ml)
  8. extractionThe solution was extracted with ether (3×50 ml)
  9. extractionThe aqueous solution was extracted with chloroform (3×100 ml)
  10. dry with materialthe chloroform extracts were dried (K2CO3 and chloroform
  11. customwas removed under reduced pressure
  12. customto give a pale brown oil, (16.22 g)
  13. customThis oil was purified by column chromatography (Kieselgel 60 70-230 mesh silica)
  14. additionThe fractions containing the desired product
  15. customwere collected
  16. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-859b3d9b1d004deb81abb1ce12c60265
Source dataset
uspto-grants-1989_02
Patent number
US04808589

Reaction notes

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