Toluene → 3-Amino-6-chloro-2-(2-furanyl)-4-methylpyridine

HRID 887712Notes

Reaction equation

HRID 887712 reaction equation
[NH2:1][C:2]1[C:3](I)=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[CH3:8].[O:11]1[CH:15]=[CH:14][CH:13]=[C:12]1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].C1(C)C=CC=CC=1>O.C1COCC1>[NH2:1][C:2]1[C:3]([C:12]2[O:11][CH:15]=[CH:14][CH:13]=2)=[N:4][C:5]([Cl:9])=[CH:6][C:7]=1[CH3:8]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2734357Furan-2-boronic acidHCID 593552676-Chloro-2-iodo-4-methylpyridin-3-amine

Product 1

HCID 593554283-Amino-6-chloro-2-(2-furanyl)-4-methylpyridineYield 86.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

3-Amino-6-chloro-2-iodo-4-methylpyridine (1.38 g), 2-furanboronic acid (861 mg), and sodium carbonate (815 mg) were suspended in a solvent mixture consistent of toluene (19 mL), THF (19 mL) and water (6 mL). The mixture was degassed using subsequent evaporation and flushing with nitrogen (5×) and tetrakis(triphenylphosphine)palladium(0) (658 mg) was added. The reaction mixture was stirred at 90° C. for 5 hours and 12 hours at room temperature. After addition of another portion of 2-furanboronic acid (430 mg) and tetrakis(triphenyl phosphine)palladium(0) (132 mg), the mixture was stirred again for 12 hours at 90° C. After 12 hours stirring at room temperature, the reaction mixture was quenched with water and extracted 2× with ethyl acetate. The combined organic layer was washed with brine, dried over MgSO4 and concentrated in vacuum. The residue was purified by column chromatography (silica 60, hexane/ethyl acetate=4:1, Rf=0.25) to afford 929 mg of the title compound of the formula

Workup

  1. customThe mixture was degassed
  2. customevaporation
  3. customflushing with nitrogen (5×) and tetrakis(triphenylphosphine)palladium(0) (658 mg)
  4. additionwas added
  5. additionAfter addition of another portion of 2-furanboronic acid (430 mg) and tetrakis(triphenyl phosphine)palladium(0) (132 mg)
  6. stirringthe mixture was stirred again for 12 hours at 90° C
  7. stirringAfter 12 hours stirring at room temperature
  8. customthe reaction mixture was quenched with water
  9. extractionextracted 2× with ethyl acetate
  10. washThe combined organic layer was washed with brine
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuum
  13. customThe residue was purified by column chromatography (silica 60, hexane/ethyl acetate=4:1, Rf=0.25)

Sources & evidence

ORD record
ord-22b3a3ab5978453b88cfad97d39eca0d
Source dataset
uspto-grants-2012_08
Patent number
US08247431B2

Reaction notes

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