o-Vanillin → 2-[(Pyridin-4-yl)carbonyl]-7-methoxybenzofuran

HRID 582506

Reaction equation

HRID 582506 reaction equation
[OH-].[Na+].O=[CH:4][C:5]1[CH:13]=[CH:12][CH:11]=[C:8]([O:9][CH3:10])[C:6]=1[OH:7].Br[CH2:15][C:16]([C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1)=[O:17]>C(O)C>[CH3:10][O:9][C:8]1[C:6]2[O:7][C:15]([C:16]([C:18]3[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=3)=[O:17])=[CH:4][C:5]=2[CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 8991o-VanillinHCID 14798Sodium HydroxideHCID 4070312-Bromo-1-(pyridin-4-yl)ethanone

Product 1

HCID 218330612-[(Pyridin-4-yl)carbonyl]-7-methoxybenzofuranYield 27%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
55 °C

Procedure

Sodium hydroxide (1.22 g) was added to a solution of o-vanillin (2.11 g) in ethanol (50 ml) at 55° C. under a nitrogen atmosphere. The reaction mixture was stirred for 10 minutes to give a yellow suspension. 4-(Bromoacetyl)pyridine hydrobomide (5 g) was then added portionwise and the solution heated at 55° C. for 12 h, then at 65-70° C. for a further 12 h. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. The residue was partitioned between water (250 ml, containing sodium hydroxide (0.5 g)) and dichloromethane (2×200 ml). The combined organic phases were washed with water (100 ml), dried over magnesium sulphate, filtered and evaporated in vacuo onto silica gel. The compound was washed through a pad of silica with ethyl acetate, the ethyl acetate was removed in vacuo and the residue azeotroped with hexane. The resulting solid was washed with hexane and filtered to furnish the title compound (0.95 g) as a yellow solid. TLC Rf 0.53 (ethyl acetate)

Workup

  1. customto give a yellow suspension
  2. waitat 65-70° C. for a further 12 h
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customthe solvent removed in vacuo
  5. customThe residue was partitioned between water (250 ml, containing sodium hydroxide (0.5 g)) and dichloromethane (2×200 ml)
  6. washThe combined organic phases were washed with water (100 ml)
  7. dry with materialdried over magnesium sulphate
  8. filtrationfiltered
  9. customevaporated in vacuo onto silica gel
  10. washThe compound was washed through a pad of silica with ethyl acetate
  11. customthe ethyl acetate was removed in vacuo
  12. customthe residue azeotroped with hexane
  13. washThe resulting solid was washed with hexane
  14. filtrationfiltered

Sources & evidence

ORD record
ord-79eb49e33a8e4770b28822b66dbaf9eb
Source dataset
uspto-grants-1999_07
Patent number
US05925636

Linked notes

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