Sodium Carbonate → 4-[4-Methoxy-3-(phenyl)phenyl]pyridine

HRID 1595252Notes

Reaction equation

HRID 1595252 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:16]1(B(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C(=O)([O-])[O-].[Na+].[Na+]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:9][O:8][C:7]1[CH:6]=[CH:5][C:4]([C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:3][C:2]=1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 66827Phenylboronic AcidHCID 80271Tri-o-tolylphosphineHCID 184760964-(3-Bromo-4-methoxyphenyl)pyridine

Product 1

HCID 99033374-[4-Methoxy-3-(phenyl)phenyl]pyridine

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 4-(3-bromo-4-methoxyphenyl)pyridine (1.32 g, 5 mmol), phenylboronic acid (0.67 g 5.5 mmol), tri-o-tolylphosphine (0.152 g, 0.50 mmol), palladium (II) acetate (0.056 g, 0.25 mmol), sodium carbonate (1.06 g, 10 mmol) and water (10 mL) in dimethylformamide (20 mL) is heated at 80° C. for 3 h. The mixture is then treated with water (100 mL) and extracted with ethyl acetate (3×80 mL). The combined extracts are washed (saturated NaCl, dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by chromatography (silica gel, 98% ethyl acetate/1.8% ethanol/0.2% aqueous NH3(25%)) to give 4-[4-methoxy-3-(phenyl)phenyl]pyridine base. The base is dissolved in diethylether (5 mL), treated with methanolic HCl (excess), evaporated to dryness under reduced pressure and recrystallised from isopropanol-diethylether to give 4-[2-methoxy-(1,1-biphenyl)-5-yl]pyridine, hydrochloride as a pale-yellow crystalline solid, m.p. 180-200° C., and having the following physical characteristics:

Workup

  1. extractionextracted with ethyl acetate (3×80 mL)
  2. washThe combined extracts are washed (saturated NaCl
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. customthe solvent is evaporated off under reduced pressure
  6. customto yield the crude product which
  7. customis purified by chromatography (silica gel, 98% ethyl acetate/1.8% ethanol/0.2% aqueous NH3(25%))

Sources & evidence

ORD record
ord-7a0c0108a6dd4703b36b70a07ac4f185
Source dataset
uspto-grants-2001_09
Patent number
US06288092B1

Reaction notes

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