4,7-Dichloroquinoline → 7-Chloro-4-[(4-fluorophenyl)methyl]quinoline

HRID 1885532Notes

Reaction equation

HRID 1885532 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]#N)=[CH:4][CH:3]=1.[NH2-].[Na+].ClC1[C:23]2[C:18](=[CH:19][C:20]([Cl:24])=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1>C1C=CC=CC=1.C(O)CCC.Cl>[Cl:24][C:20]1[CH:19]=[C:18]2[C:23]([C:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:15][CH:16]=[N:17]2)=[CH:22][CH:21]=1

Participants

7

Reactant 3

HCID 68664,7-DichloroquinolineHCID 24533Sodium amideHCID 68016Benzeneacetonitrile, 4-fluoro-

Product 1

HCID 1641757-Chloro-4-[(4-fluorophenyl)methyl]quinolineYield 67%

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 2631-ButanolSolventHCID 313Hydrochloric AcidSolvent

Procedure

A solution of 100 g (740 mmol) of 4-fluorophenylacetonitrile in 200 ml of benzene was added to a cooled (0° C.) slurry of 40 g (945 mmol) of sodium amide in 600 ml of the same solvent. After the addition was complete the solution was warmed to ambient temperature and stirred for one-half hour. The reaction mixture was again cooled to 0° C., 73.2 g (370 mmol) of solid 4,7-dichloroquinoline was added in increments, and the mixture was then stirred at ambient temperature overnight. Quenching with NH4Cl followed by workup gave the crude disubstituted acetonitrile, which was dissolved in 500 ml of n-butanol saturated with anhydrous HCl. The acidic solution was heated at reflux for 18 hours. The majority of the solvent was removed via distillation, and the residue was diluted with solvent, and washed with 10% NaOH. The organic layer was dried, and the solvent was removed in vacuo. Purification via HPLC gave 67 g of the title product. Yield: 67%.

Workup

  1. additionAfter the addition
  2. temperatureThe reaction mixture was again cooled to 0° C.
  3. stirringthe mixture was then stirred at ambient temperature overnight
  4. customQuenching with NH4Cl
  5. customgave the crude disubstituted acetonitrile, which
  6. temperatureThe acidic solution was heated
  7. temperatureat reflux for 18 hours
  8. customThe majority of the solvent was removed via distillation
  9. additionthe residue was diluted with solvent
  10. washwashed with 10% NaOH
  11. customThe organic layer was dried
  12. customthe solvent was removed in vacuo
  13. customPurification via HPLC

Sources & evidence

ORD record
ord-99ff8803823d455bafeacac8adfeb048
Source dataset
uspto-grants-1992_09
Patent number
US05145843

Reaction notes

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