Phenylacetonitrile → 2-Phenyl-(3-pyridyl)-4-(2-azabicyclo[2.2.2]oct-2-yl)butyronitrile

HRID 1415154Notes

Reaction equation

HRID 1415154 reaction equation
[CH2:1]([C:8]#[N:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1.[NH2-].[Na+].Cl[CH2:20][CH2:21][N:22]1[CH2:27][CH:26]2[CH2:28][CH2:29][CH:23]1[CH2:24][CH2:25]2>CCOCC.O.C1(C)C=CC=CC=1>[C:2]1([C:1]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)([CH2:20][CH2:21][N:22]2[CH2:27][CH:26]3[CH2:28][CH2:29][CH:23]2[CH2:24][CH2:25]3)[C:8]#[N:9])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8794PhenylacetonitrileHCID 122863-BromopyridineHCID 24533Sodium amideHCID 126123252-(2-Chloroethyl)-2-azabicyclo[2.2.2]octane

Product 1

HCID 203569662-Phenyl-(3-pyridyl)-4-(2-azabicyclo[2.2.2]oct-2-yl)butyronitrile

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 25 parts of benzyl cyanide, 35 parts of 3-bromopyridine and 220 parts of dry toluene is heated to 80° C. with stirring. Then, 19 parts of sodamide is added portionwise over a period of 1 hour while the temperature is maintained at 80°-85° C. with some cooling. The resultant mixture is heated to 105° C. and a solution of 56 parts of 2-(2-chloroethyl)-2-azabicyclo[2.2.2]octane in 220 parts of dry toluene is added portionwise. The mixture is then heated at 105°-110° C. for an additional 3 hours before it is cooled and 250 parts of water is added. The organic layer is separated and dried and the solvent is evaporated to leave a residue which is dissolved in ether and filtered. The ether solvent is evaporated from the filtrate and the residual oil is distilled under reduced pressure to provide 2-phenyl-2-(3-pyridyl)-4-(2-azabicyclo[2.2.2]oct-2-yl)butyronitrile. Alternately α-phenyl-3-pyridylacetonitrile (U.S. Pat. No. 3,225,054) is reacted with 2-(2-chloroethyl)-2-azabicyclo[2.2.2]octane directly.

Workup

  1. temperatureis maintained at 80°-85° C. with some cooling
  2. temperatureThe mixture is then heated at 105°-110° C. for an additional 3 hours before it
  3. temperatureis cooled
  4. customThe organic layer is separated
  5. customdried
  6. customthe solvent is evaporated
  7. customto leave a residue which
  8. filtrationfiltered
  9. customThe ether solvent is evaporated from the filtrate
  10. distillationthe residual oil is distilled under reduced pressure

Sources & evidence

ORD record
ord-fa463c9188d34fb0989a0999a20f94fa
Source dataset
uspto-grants-1977_01
Patent number
US04003904

Reaction notes

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