Sodium Carbonate → 2,3-Dichloro-4-(4-methylphenyl)pyridine

HRID 2101274Notes

Reaction equation

HRID 2101274 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[C:6](I)[CH:5]=[CH:4][N:3]=1.[CH3:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.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>[Cl:1][C:2]1[C:7]([Cl:8])=[C:6]([C:14]2[CH:15]=[CH:16][C:11]([CH3:10])=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 79799Tolylboronic acidHCID 448870382,3-Dichloro-4-iodopyridine

Product 1

HCID 577994252,3-Dichloro-4-(4-methylphenyl)pyridineYield 98.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2,3-dichloro-4-iodopyridine (1.92 g, 7.0 mmol) in toluene (20 mL) at room temperature under argon was added 4-methylphenylboronic acid (1.05 g, 7.7 mmol), tetrakis(triphenylphosphine)palladium (0.40 g, 0.35 mmol), and aqueous Na2CO3 solution (2.0 M, 7 mL, 14 mmol). The resulting suspension was stirred and heated at 100° C. under argon for 5 h. Analysis by HPLC/MS indicated that starting material had been consumed. After the reaction mixture was cooled to room temperature, water (25 mL) and EtOAc (30 mL) were added. The layers were separated. The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes) to obtain 1.64 g of the title compound as a white solid. HPLC/MS: retention time=3.77 min, [M+H]+=238. 1H NMR (CDCl3): δ 8.30 (d, J=4.9 Hz, 1H), 7.34-7.29 (m, 4H), 7.20 (d, J=4.9 Hz, 1H), 2.43 (s, 3H).

Workup

  1. customhad been consumed
  2. temperatureAfter the reaction mixture was cooled to room temperature
  3. additionwater (25 mL) and EtOAc (30 mL) were added
  4. customThe layers were separated
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by automated silica gel chromatography (eluted with ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-eb75b463f7d74e6f9709a8ff969414be
Source dataset
uspto-grants-2009_08
Patent number
US07572808B2

Reaction notes

Loading…