Ethyl Acetate → 3-Bromo-2-chloro-4-(4-chlorophenyl)pyridine

HRID 2101298Notes

Reaction equation

HRID 2101298 reaction equation
[Br:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[CH:6][C:7]=1I.[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>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:14]1[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 407869003-Bromo-2-chloro-4-iodopyridine

Product 1

HCID 577993673-Bromo-2-chloro-4-(4-chlorophenyl)pyridineYield 38.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of crude 3-bromo-2-chloro-4-iodopyridine (10.0 g, 31.41 mmol) in toluene (120 mL) at room temperature under argon was added 4-chlorophenylboronic acid (5.8 g, 37.1 mmol), tetrakis(triphenylphosphine)palladium (2.2 g, 1.9 mmol), and a solution of Na2CO3 (6.6 g, 62.3 mmol) in water (20 mL). The resulting suspension was stirred and heated at 100° C. under argon for 2.5 h. After the reaction mixture was cooled to room temperature, water (120 mL) and EtOAc (150 mL) were added. The layers were separated. The organic layer was dried (MgSO4), filtered, and concentrated under reduced pressure. The crude product was purified by flash chromatography (silica gel column eluting with 7% ethyl acetate-hexanes) to isolate 3.7 g of the title compound as a white solid. HPLC/MS: retention time=3.78 min, [M+H]+=302. 1H NMR (CDCl3, 500 MHz): δ 8.35 (d, J=5.0 Hz, 1H), 7.46 (d, J=10.0 Hz, 2H), 7.34 (d, J=10.0 Hz, 2H), 7.14 (d, J=5.0 Hz, 1H).

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by flash chromatography (silica gel column eluting with 7% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-777cde5ba39f4c21b3e54bc59dc9e834
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

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