Potassium Carbonate → 2-(5-Chloro-2-methoxyphenyl)pyridin-3-amine

HRID 1514014Notes

Reaction equation

HRID 1514014 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6](B(O)O)[CH:7]=1.[NH2:13][C:14]1[C:15](Cl)=[N:16][CH:17]=[CH:18][CH:19]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[K+].[K+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:11][CH3:12])=[C:6]([C:15]2[C:14]([NH2:13])=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:7]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 805282-Chloro-3-pyridylamineHCID 27357515-Chloro-2-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenyl

Product 1

HCID 687348122-(5-Chloro-2-methoxyphenyl)pyridin-3-amine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent

Procedure

The 500 mL round-bottom flask, equipped with magnetic stirrer and reflux condenser was charged with 5-chloro-2-methoxyphenylboronic acid (9.78 g, 52 mmol), 3-amino-2-chloropyridine (7.00 g, 55 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (S-Phos, 0.43 g, 2 mol %), palladium (II) acetate (112 mg, 1 mol %), potassium carbonate (21.7 g, 157 mmol), 180 mL of acetonitrile and 20 ml of water. The flask was filled with nitrogen and heated to reflux under nitrogen atmosphere for 24 hours. Then the reaction was cooled down to room temperature, diluted with 500 mL of water and extracted with ethyl acetate (5×40 mL). Organic fractions were combined, dried over sodium sulfate, filtered and evaporated. The residue was subjected to column chromatography on silica gel with eluent hexane/ethyl acetate gradient mixture, providing 2-(5-chloro-2-methoxyphenyl)pyridin-3-amine as white crystals (9.5 g, NMR confirmed the structure).

Workup

  1. customThe 500 mL round-bottom flask, equipped with magnetic stirrer
  2. temperaturereflux condenser
  3. additionThe flask was filled with nitrogen
  4. temperatureheated
  5. temperatureto reflux under nitrogen atmosphere for 24 hours
  6. extractionextracted with ethyl acetate (5×40 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customevaporated

Sources & evidence

ORD record
ord-7b2ade70cd0c43f5b65ba332df0f3cb6
Source dataset
uspto-grants-2012_07
Patent number
US08221905B2

Reaction notes

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