Potassium Phosphate, Tribasic → 5-(2-Chlorophenyl)-4-(4-chlorophenyl)-2-fluoropyridine

HRID 1867888Notes

Reaction equation

HRID 1867888 reaction equation
Cl[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[C:3]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 27343222-Chlorophenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 577994555-Chloro-4-(4-chlorophenyl)-2-fluoropyridine

Product 1

HCID 577994125-(2-Chlorophenyl)-4-(4-chlorophenyl)-2-fluoropyridineYield 35.4%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
95 °C

Procedure

To a flame-dried tube was placed 5-chloro-4-(4-chlorophenyl)-2-fluoropyridine (0.71 g, 2.93 mmol), 2-chlorophenylboronic acid (0.55 g, 3.52 mmol), K3PO4 (1.24 g, 5.86 mmol), Pd2(dba)3 (0.134 g, 0.147 mmol), and S-Phos (0.12 g, 0.29 mmol). The reaction vessel was then purged with argon three times before degassed toluene (15 mL) was added in, and sealed. The reaction mixture was stirred at 95° C. for 16 h. Analysis by HPLC/MS indicated the reaction was complete. After cooling to room temperature, the reaction mixture was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc (30 mL×3). The combined organic was washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (80 g) eluting with a gradient of EtOAc (0-10%) in hexanes to afford 0.33 g (35%) of the title compound as a white foam. HPLC/MS: retention time=4.03 min, [M+H]+=318.1.

Workup

  1. customTo a flame-dried tube was placed
  2. customThe reaction vessel was then purged with argon three times
  3. custombefore degassed toluene (15 mL)
  4. additionwas added in, and
  5. customsealed
  6. temperatureAfter cooling to room temperature
  7. customthe reaction mixture was partitioned between EtOAc and water
  8. extractionThe aqueous layer was extracted with EtOAc (30 mL×3)
  9. washThe combined organic was washed with saturated aqueous NaCl
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product was purified
  14. washeluting with a gradient of EtOAc (0-10%) in hexanes

Sources & evidence

ORD record
ord-98bde97775f643dd90650f3f925ded95
Source dataset
uspto-grants-2009_12
Patent number
US07632837B2

Reaction notes

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