3-Hydroxybenzaldehyde → Benzaldehyde, 3-(4-fluorophenoxy)-

HRID 1889693Notes

Reaction equation

HRID 1889693 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[F:10][C:11]1[CH:16]=[CH:15][C:14](Br)=[CH:13][CH:12]=1.C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1.[Cu]>[F:10][C:11]1[CH:16]=[CH:15][C:14]([O:1][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[CH:5]=[O:6])=[CH:13][CH:12]=1

Participants

6

Reactant 3

HCID 1013-HydroxybenzaldehydeHCID 99931-Bromo-4-fluorobenzeneHCID 11430Potassium Carbonate

Product 1

HCID 3085320Benzaldehyde, 3-(4-fluorophenoxy)-Yield 35%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 1049PyridineSolvent

Procedure

To a mixture of 3-hydroxybenzaldehyde (5.0 g, 40.9 mmol, 1.0 eq) and 4-fluorobromobenzene (14.3 g, 81.7 mmol, 2 eq) in pyridine was added K2CO3 (8.5 g, 61.4 mmol, 1.5 eq) followed by copper powder (1.3 g, 20.5 mmol, 0.5 eq). The reaction mixture was refluxed for 60 h before being filtered to remove the copper powder. The filtrate was then distilled under reduced pressure to remove pyridine. The resultant residue was taken in ethyl acetate and washed with water. The organic layer was dried over anhydrous Na2SO4 and concentrated under in vacuo. The residue was purified by silica gel column chromatography eluting with 10-20% ethyl acetate in hexane to afford the desired compound (3.0 g, 35%). 1H NMR (400 MHz, CDCl3) δ 9.96 (s, 1H), 7.61-7.58 (t, 1H), 7.50-7.48 (t, 1H), 7.42-7.41 (t, 1H), 7.28-7.24 (m, 1H), 7.11-6.99 (m, 4H). MS (ESI): 218.0 (M+H)+.

Workup

  1. temperatureThe reaction mixture was refluxed for 60 h
  2. filtrationbefore being filtered
  3. customto remove the copper powder
  4. distillationThe filtrate was then distilled under reduced pressure
  5. customto remove pyridine
  6. washwashed with water
  7. dry with materialThe organic layer was dried over anhydrous Na2SO4
  8. concentrationconcentrated under in vacuo
  9. customThe residue was purified by silica gel column chromatography
  10. washeluting with 10-20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-cc30f93c7b5c45929a1b4d4dd0794a1d
Source dataset
uspto-grants-2013_08
Patent number
US08501992B2

Reaction notes

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