Potassium Carbonate → 4-(4-Phenyl-3,6-dihydropyridin-1(2H)-yl)butanenitrile

HRID 1602921Notes

Reaction equation

HRID 1602921 reaction equation
Cl.[C:2]1([C:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH:13]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:21][CH2:22][CH2:23][C:24]#[N:25]>C(#N)C>[C:2]1([C:8]2[CH2:13][CH2:12][N:11]([CH2:21][CH2:22][CH2:23][C:24]#[N:25])[CH2:10][CH:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 214124-BromobutyronitrileHCID 27238604-Phenyl-1,2,3,6-tetrahydropyridine hydrochloride

Product 1

HCID 214951844-(4-Phenyl-3,6-dihydropyridin-1(2H)-yl)butanenitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

5 g of 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (very toxic compound: New Engl. J. Med., 1983, 309, 310; Science, 1983, 219, 979; Psychiatry Res., 1979, 1, 249) and then 100 ml of acetonitrile are introduced into a 250 ml round-bottomed flask. 2.5 equivalents of anhydrous potassium carbonate are added and then 1.05 equivalents of 4-bromobutyronitrile, in solution in acetonitrile, are added dropwise. The mixture is heated at reflux for 16 hours and then filtered, the precipitate is washed with acetone and the filtrate is concentrated. The residue is taken up in ethyl acetate and washed 3 times with water. The organic phase is extracted with a 3M hydrochloric acid solution and the acid phase is washed with ethyl acetate. The acid phase is neutralized with 28% aqueous ammonia to pH>11. Extraction is carried out with ethyl acetate, the organic phase is washed with water and dried over anhydrous sodium sulphate and the mixture is concentrated. The nitrile is purified by chromatography on a silica column (eluent: ethyl acetate/hexane 80/20). White crystals are obtained. M.p.=57-59° C. Y=79%. 1H NMR (CDCl3, 330K): 1.81-1.95 (m, 2H, --CH2 --, 2.40-2.48 (t, 2H, --CH2 --), 2.54-2.60 (t, 4H, --H2C--CH2 --), 2.67-2.72 (t, 2H, --CH2 --), 3.12-3.17 (q, 2H, --CH2 --), 6.06-6.09 (m, 1H, --CH=), 7.24-7.44 (m, 5H, phe). 13C NMR (CDCl3): 14.7 (--CH2 --CH2 --C≡N), 22.8 (--CH2 --C≡N), 27.7 (>C--CH2 --CH2 --N<, pyrid), 50.0 (--CH2 --CH2 --N<, pyrid), 52.9 (=CH--CH2 --N<, pyrid), 55.9 (>N--CH2 --), 119.6 (--CN), 121.3 (>CH--), 124.6 (=CH--, pyri), 126.8 (>(CH)2 --), 128.1 (>CH)2 --), 134.7 (>C=C--, pyri), 140.4 (>C<).

Workup

  1. temperatureThe mixture is heated
  2. temperatureat reflux for 16 hours
  3. filtrationfiltered
  4. washthe precipitate is washed with acetone
  5. concentrationthe filtrate is concentrated
  6. washwashed 3 times with water
  7. extractionThe organic phase is extracted with a 3M hydrochloric acid solution
  8. washthe acid phase is washed with ethyl acetate
  9. extractionExtraction
  10. washthe organic phase is washed with water
  11. dry with materialdried over anhydrous sodium sulphate
  12. concentrationthe mixture is concentrated
  13. customThe nitrile is purified by chromatography on a silica column (eluent: ethyl acetate/hexane 80/20)
  14. customWhite crystals are obtained

Sources & evidence

ORD record
ord-832e801035904a7081eb28573c4807e1
Source dataset
uspto-grants-1999_11
Patent number
US05985895

Reaction notes

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