Water → 4-cyano-N-(4-propoxyphenylmethyl)piperidine

HRID 866054Notes

Reaction equation

HRID 866054 reaction equation
[NH2:1][C:2]([CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH2:18][CH2:19][CH3:20])=[CH:13][CH:12]=2)[CH2:6][CH2:5]1)=O.[Cl-].[Na+].P(Cl)(Cl)(Cl)=O.O>ClCCCl>[C:2]([CH:4]1[CH2:9][CH2:8][N:7]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][CH2:18][CH2:19][CH3:20])=[CH:15][CH:16]=2)[CH2:6][CH2:5]1)#[N:1]

Participants

6

Reactant 4

HCID 962WaterHCID 5234Sodium ChlorideHCID 24813Phosphorus oxychlorideHCID 190409324-aminocarbonyl-N-(4-propoxyphenylmethyl)piperidine

Product 1

HCID 190409134-cyano-N-(4-propoxyphenylmethyl)piperidineYield 56.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of 27.0 grams (0.10 mole) of 4-aminocarbonyl-N-(4-propoxyphenylmethyl)piperidine in 200 mL of 1,2-dichloroethane was stirred at ambient temperature, and 8.0 grams (0.14 mole) of sodium chloride, followed by 9.2 grams (0.06 mole) of phosphorous oxychloride were added. The reaction mixture was then warmed to reflux, where it stirred for about 1.75 hours. The reaction mixture was cooled to ambient temperature and about 350 mL of water was added. The aqueous layer was separated, washed with two portions of diethyl ether, and then made basic with aqueous 5% sodium hydroxide. The mixture was extracted with two portions of diethyl ether. The combined extracts were washed with an aqueous solution saturated with sodium chloride. The organic layer was dried with sodium sulfate and poured through a pad of silica gel. The silica gel pad was washed with 1000 mL of diethyl ether. The combined eluants were concentrated under reduced pressure, yielding 14.5 grams of 4-cyano-N-(4-propoxyphenylmethyl)piperidine. The NMR spectrum was consistent with the proposed structure.

Workup

  1. additionwere added
  2. temperatureThe reaction mixture was then warmed
  3. temperatureto reflux
  4. stirringwhere it stirred for about 1.75 hours
  5. temperatureThe reaction mixture was cooled to ambient temperature
  6. customThe aqueous layer was separated
  7. washwashed with two portions of diethyl ether
  8. extractionThe mixture was extracted with two portions of diethyl ether
  9. washThe combined extracts were washed with an aqueous solution saturated with sodium chloride
  10. dry with materialThe organic layer was dried with sodium sulfate
  11. additionpoured through a pad of silica gel
  12. washThe silica gel pad was washed with 1000 mL of diethyl ether
  13. concentrationThe combined eluants were concentrated under reduced pressure

Sources & evidence

ORD record
ord-f90e01630c18444380480542283994c6
Source dataset
uspto-grants-1996_10
Patent number
US05569664

Reaction notes

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