Potassium Carbonate → 2-Chloro-4-(2-methoxyphenyl)pyridine

HRID 593276Notes

Reaction equation

HRID 593276 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([Cl:8])[CH:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>COCCOC.O.C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:4]1[CH:3]=[C:2]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH3:9])[CH:7]=[CH:6][N:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 38477704-Bromo-2-chloropyridine

Product 1

HCID 584326112-Chloro-4-(2-methoxyphenyl)pyridineYield 52.5%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6344DichloromethaneSolventHCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

To a solution of 4-bromo-2-chloro-pyridine (1.0 g, 5.2 mmol) in DME/water 10:1 (15 mL) was added (2-methoxyphenyl)boronic acid (0.79 g, 5.2 mmol), Pd(PPh3)2Cl2 (240 mg, 0.34 mmol), and K2CO3 (1.8 g, 13.0 mmol). The mixture was heated with reflux for 6 hours. It was diluted with DCM, washed three times with water, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, DCM/MeOH 100:0 to 90:10) to give the title compound A1 (0.6 g, 52%). MS (ES) C12H10ClNO requires: 219. found: 220 (M+H)+.

Workup

  1. temperatureThe mixture was heated
  2. temperaturewith reflux for 6 hours
  3. washwashed three times with water
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash chromatography (silica gel, DCM/MeOH 100:0 to 90:10)

Sources & evidence

ORD record
ord-9a43003296804426ac74d861833e89ec
Source dataset
uspto-grants-2016_01
Patent number
US09242937B2

Reaction notes

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