Cesium carbonate → 2-Methoxy-5-(pyridin-3-yl)benzaldehyde

HRID 2389712Notes

Reaction equation

HRID 2389712 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10])=[O:2].Br[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C>[CH3:10][O:9][C:8]1[CH:7]=[CH:6][C:5]([C:15]2[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=2)=[CH:4][C:3]=1[CH:1]=[O:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 122863-BromopyridineHCID 2759225(3-Formyl-4-methoxyphenyl)boronic acid

Product 1

HCID 226200772-Methoxy-5-(pyridin-3-yl)benzaldehydeYield 32%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Procedure

N1 is prepared according to a method similar to Method A. Commercially available 3-formyl-4-methoxyphenylboronic acid (1.66 g, 9.22 mmol) is dissolved in 56 mL toluene and 14 mL ethanol. 3-Bromopyridine (0.98 mL, 10.2 mmol) is added followed by cesium carbonate (3.0 g, 9.21 mmol). Nitrogen is bubbled through the mixture for 10 minutes, then palladium tetrakistriphenylphosphine (0.53 g, 0.46 mmol) is added and nitrogen bubbling is resumed for another ten minutes. The mixture is heated to reflux for 5 hours. The mixture is allowed to cool and is filtered through Celite. The Celite pad is washed with ethyl acetate and methylene chloride. The filtrate is pumped dry and the residue is chromatographed on silica gel using a gradient elution of methanol/methylene chloride. 2-Methoxy-5-pyridin-3-yl-benzaldehyde (N1) is obtained (0.635 g, 2.98 mmol; 32% yield).

Workup

  1. customN1 is prepared
  2. customNitrogen is bubbled through the mixture for 10 minutes
  3. waitnitrogen bubbling is resumed for another ten minutes
  4. temperatureThe mixture is heated
  5. temperatureto reflux for 5 hours
  6. temperatureto cool
  7. filtrationis filtered through Celite
  8. washThe Celite pad is washed with ethyl acetate and methylene chloride
  9. customThe filtrate is pumped dry
  10. customthe residue is chromatographed on silica gel using
  11. washa gradient elution of methanol/methylene chloride

Sources & evidence

ORD record
ord-223c6bd7cef242d4a063e191d3fe6230
Source dataset
uspto-grants-2012_09
Patent number
US08273747B2

Reaction notes

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