2-Chloro-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)nicotinonitrile → 5-(4-Chlorophenyl)-6-(2,4-dichlorophenyl)-2-(3,4-difluorobenzyl)nicotinonitrile

HRID 916940

Reaction equation

HRID 916940 reaction equation
Cl[C:2]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=2[Cl:17])[C:7]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:6][C:3]=1[C:4]#[N:5].[Br-].[F:26][C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][C:34]=1[F:35])[CH2:30][Zn+]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:7]2[C:8]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][C:11]=3[Cl:17])=[N:9][C:2]([CH2:30][C:29]3[CH:32]=[CH:33][C:34]([F:35])=[C:27]([F:26])[CH:28]=3)=[C:3]([CH:6]=2)[C:4]#[N:5])=[CH:23][CH:22]=1

Participants

5

Reactant 2

HCID 101506772-Chloro-5-(4-chlorophenyl)-6-(2,4-dichlorophenyl)nicotinonitrileHCID 178505766HCID 178505766, compound

Product 1

HCID 102175615-(4-Chlorophenyl)-6-(2,4-dichlorophenyl)-2-(3,4-difluorobenzyl)nicotinonitrile

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

To a dried round bottom flask was added THF (1 mL), the product of Example 36 (0.050 g; 0.127 mmol), 3,4-diflourobenzylzinc bromide (0.27 mL of a 0.5 M solution in THF; 0.134 mmol), and tetrakis(triphenylphosphine) palladium (0) (0.008 g; 5 mol %). The reaction was evacuated and purged with nitrogen several times and stirred at 50° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and washed with saturated aq. NaHCO3 solution (3×), and brine. The organic portion was dried (Na2SO4), filtered, and concentrated in vacuo. Purification done by MPLC (silica gel; 0-10% ethyl acetate/hexane gradient) afforded the desired product: m/e=487 (M+3); Rt=4.8 min.

Workup

  1. customThe reaction was evacuated
  2. custompurged with nitrogen several times
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate
  5. washwashed with saturated aq. NaHCO3 solution (3×), and brine
  6. dry with materialThe organic portion was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification

Sources & evidence

ORD record
ord-9e475539642041de812820d7645776ff
Source dataset
uspto-grants-2007_09
Patent number
US07271266B2

Linked notes

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