Potassium Carbonate → 2-Chloro-6-(3-methoxyphenyl)pyridine

HRID 385311Notes

Reaction equation

HRID 385311 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15](Cl)[N:14]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O.C(COC)OC>[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([C:5]2[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=2)[N:14]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 169892,6-DichloropyridineHCID 2734370(3-Methoxyphenyl)boronic acid

Product 1

HCID 594893042-Chloro-6-(3-methoxyphenyl)pyridine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of m-methoxy-phenylboronic acid (10 g, 65.8 mmol), 2,6-dichloropyridine (9.7 g, 65.8 mmol), potassium carbonate (27.3 g, 197.4 mmol), triphenylphosphine (2.07 g., 7.9 mmol), dimethoxyethane 250 mL and water 80 mL was prepared. Nitrogen was bubbled directly in the mixture for 20 minutes. Then palladium acetate was added (0.44 g, 2.0 mmol). Nitrogen was bubbled again in the mixture for another minutes. The mixture was heated to reflux under nitrogen overnight. The reaction mixture was cooled to room temperature. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and evaporated. The mixture was purified by silica column with up to 10% ethyl acetate in hexanes to gain 6.5 g colorless oil (45%).

Workup

  1. customwas prepared
  2. customNitrogen was bubbled directly in the mixture for 20 minutes
  3. additionThen palladium acetate was added (0.44 g, 2.0 mmol)
  4. customNitrogen was bubbled again in the mixture for another minutes
  5. temperatureThe mixture was heated
  6. temperatureto reflux under nitrogen overnight
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with dichloromethane
  9. dry with materialThe combined organic layers were dried over magnesium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customThe mixture was purified by silica column with up to 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-91137b48df37454d899bd6394dc41ac5
Source dataset
uspto-grants-2013_02
Patent number
US08367850B2

Reaction notes

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