4-Hydroxybenzaldehyde → 4-(2-(Piperidin-1-yl)ethoxy)benzaldehyde

HRID 1449742Notes

Reaction equation

HRID 1449742 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.Cl.Cl[CH2:12][CH2:13][CH:14]1CCNCC1.[C:20](=O)([O-])[O-].[K+].[K+].[CH3:26][N:27]([CH:29]=O)[CH3:28]>>[N:27]1([CH2:29][CH2:20][O:1][C:2]2[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=2)[CH2:28][CH2:14][CH2:13][CH2:12][CH2:26]1

Participants

5

Reactant 4

HCID 1264-HydroxybenzaldehydeHCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 219374464-(2-Chloroethyl)piperidine hydrochloride

Product 1

HCID 111838924-(2-(Piperidin-1-yl)ethoxy)benzaldehyde

Procedure

4-Hydroxybenzaldehyde (25.0 g) and 4-(2-chloroethyl)piperadine hydrochloride (60.38 g) are dissolved in DMF (650 ml) and solid potassium carbonate (45 g) is added. The reaction is refluxed for 24 hr, cooled to 20°-25° and the DMF is removed under reduced pressure. The remainder of the reaction is dissolved in chloroform and washed with 1N aqueous sodium hydroxide, saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Purification by flash column chromatography eluting with a gradient of 50% ethyl acetate/hexane to 5% methanol/ethyl acetate, pooling and concentrating the appropriate fractions gives the title compound, NMR (300 MHz, CDCl3) 9.75, 7.69, 6.87, 4.10, 2.73, 2.45, 1.52, 1.36 δ.

Workup

  1. temperatureThe reaction is refluxed for 24 hr
  2. temperaturecooled to 20°-25°
  3. customthe DMF is removed under reduced pressure
  4. dissolutionThe remainder of the reaction is dissolved in chloroform
  5. washwashed with 1N aqueous sodium hydroxide, saline
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customPurification by flash column chromatography
  9. washeluting with a gradient of 50% ethyl acetate/hexane to 5% methanol/ethyl acetate, pooling
  10. concentrationconcentrating the appropriate fractions

Sources & evidence

ORD record
ord-3e7d441317b84e9dbdc1fb1ac4d18373
Source dataset
uspto-grants-1997_02
Patent number
US05599930

Reaction notes

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