Sodium Carbonate → 2-(5-Chloro-2-fluorophenyl)pyridin-4-amine

HRID 1522547Notes

Reaction equation

HRID 1522547 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6](B(O)O)[CH:7]=1.Cl[C:13]1[CH:18]=[C:17]([NH2:19])[CH:16]=[CH:15][N:14]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.[Pd](Cl)Cl.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:1][C:2]1[CH:3]=[CH:4][C:5]([F:11])=[C:6]([C:13]2[CH:18]=[C:17]([NH2:19])[CH:16]=[CH:15][N:14]=2)[CH:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 844322-Chloropyridin-4-amineHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acid

Product 1

HCID 674696072-(5-Chloro-2-fluorophenyl)pyridin-4-amineYield 20%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

5-Chloro-2-fluorophenylboronic acid (2.7 g, 15.48 mmol), 2-chloropyridin-4-amine (1.531 g, 11.91 mmol), sodium carbonate (5.96 ml, 11.91 mmol), and bis(triphenylphosphine) palladium chloride (0.836 g, 1.191 mmol) were combined in dioxane (54 mL) and refluxed for 3 hours. The reaction was cooled, the solvent removed in vacuo and the reaction mixture partitioned between brine and EtOAc. The organic layer was separated, dried over MgSO4 filtered and purified using NH silica column chromatography and a gradient of 5-95% EtOAc in hexanes to afford the title compound as a white solid (522 mg; 20%). ESI-MS: m/z 223.1 (M+H).

Workup

  1. temperaturerefluxed for 3 hours
  2. temperatureThe reaction was cooled
  3. customthe solvent removed in vacuo
  4. customthe reaction mixture partitioned between brine and EtOAc
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. custompurified

Sources & evidence

ORD record
ord-a58b868b655f4f409c464457c1063e99
Source dataset
uspto-grants-2015_07
Patent number
US09073918B2

Reaction notes

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