Toluene → alpha-(3-Chloropropyl)-4-fluoro-alpha-(4-fluorophenyl)benzeneacetonitrile

HRID 35307Notes

Reaction equation

HRID 35307 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)[C:9]#[N:10])=[CH:4][CH:3]=1.Br[CH2:19][CH2:20][CH2:21][Cl:22].[OH-].[Na+].CC1C=CC=CC=1>[Cl-].C([N+](CC)(CC)CC1C=CC=CC=1)C.O>[Cl:22][CH2:21][CH2:20][CH2:19][C:8]([C:11]1[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=1)([C:5]1[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=1)[C:9]#[N:10]

Participants

7

Reactant 4

HCID 1140TolueneHCID 80061-Bromo-3-chloropropaneHCID 14798Sodium HydroxideHCID 1203651Bis(4-fluorophenyl)acetonitrile

Product 1

HCID 19883501alpha-(3-Chloropropyl)-4-fluoro-alpha-(4-fluorophenyl)benzeneacetonitrileYield 95%

Reagents, catalysts & solvents 2

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolvent

Procedure

To a stirred and cooled (ice-bath) mixture of 22.9 parts of 4-fluoro-α-(4-fluorophenyl)benzeneacetonitrile, 23.6 parts of 1-bromo-3-chloropropane and 0.4 parts of N,N,N-triethylbenzenemethanaminium chloride were added dropwise 600 parts of sodium hydroxide solution 50% at a temperature below 30° C. Upon completion, stirring was continued for 3 hours at 50°-60° C. Methylbenzene and water were added and the layers were separated. The organic phase was dried, filtered and evaporated. The residue was evaporated once more in vacuo for 30 minutes at 100° C. to remove the last traces of 1-bromo-3-chloropropane, yielding 29 parts (95%) of α-(3-chloropropyl)-4-fluoro-α-(4-fluorophenyl)benzeneacetonitrile as a residue (intermediate 14).

Workup

  1. temperaturecooled
  2. stirringUpon completion, stirring
  3. customthe layers were separated
  4. customThe organic phase was dried
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was evaporated once more in vacuo for 30 minutes at 100° C.
  8. customto remove the last traces of 1-bromo-3-chloropropane

Sources & evidence

ORD record
ord-7376ac0640db4037b65ea358e2ec2057
Source dataset
uspto-grants-1988_08
Patent number
US04766125

Reaction notes

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