Toluene → 4-(3-Bromo-2-chloropyridin-4-yl)benzonitrile

HRID 2101292Notes

Reaction equation

HRID 2101292 reaction equation
[Br:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[CH:6][C:7]=1I.[C:10]([C:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1)#[N:11].C([O-])([O-])=O.[Na+].[Na+].C1(C)C=CC=CC=1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[CH:6][C:7]=1[C:15]1[CH:16]=[CH:17][C:12]([C:10]#[N:11])=[CH:13][CH:14]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium Carbonate2×HCID 27343264-Cyanophenylboronic acid2×HCID 407869003-Bromo-2-chloro-4-iodopyridine

Product 1

HCID 714279594-(3-Bromo-2-chloropyridin-4-yl)benzonitrileYield 29%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst3×HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of impure 3-bromo-2-chloro-4-iodopyridine (2.23 g), 4-cyanophenylboronic acid (1.62 g, 11.0 mmol), 2 M aqueous Na2CO3 solution (6 mL, 12 mmol), and toluene (40 mL) was purged with argon, then (Ph3P)4Pd (1.1 g, 0.95 mmol) was added in one portion. The resulting yellow mixture was vigorously stirred under argon at 100° C. for 4 h. Analysis by HPLC/MS indicated the reaction was not complete, and additional 4-cyanophenylboronic acid (0.82 g, 5.57 mmol), 2 M aqueous Na2CO3 solution (3.5 mL) and (Ph3P)4Pd (850 mg) were added. The reaction mixture was stirred at 100° C. for 12 h more. Additional (Ph3P)4Pd (1.0 g) was added, and the reaction mixture was stirred for another 20 h. After cooling to room temperature, the reaction mixture was diluted with water and extracted with EtOAc (40 mL×3). The combined EtOAc extracts were washed with water, then saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified using a silica gel cartridge (80 g) eluted with a gradient of EtOAc (0-60%) in hexanes to obtain 590 mg (29%) of the title compound as an off-white solid. HPLC/MS: retention time=3.11 min, [M+H]+=292.

Workup

  1. customwas purged with argon
  2. stirringThe reaction mixture was stirred at 100° C. for 12 h more
  3. stirringthe reaction mixture was stirred for another 20 h
  4. temperatureAfter cooling to room temperature
  5. extractionextracted with EtOAc (40 mL×3)
  6. washThe combined EtOAc extracts were washed with water
  7. dry with materialsaturated aqueous NaCl, dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified
  11. washeluted with a gradient of EtOAc (0-60%) in hexanes

Sources & evidence

ORD record
ord-3856497251cc4d43b3a325b02f0b44a2
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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