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

HRID 1604396Notes

Reaction equation

HRID 1604396 reaction equation
[N:1]1([CH:7](O)[CH3:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.OO>C1COCC1.C(OCC)C>[N:1]1([CH2:7][CH2:8][O:10][C:11]2[CH:18]=[CH:17][C:14]([CH:15]=[O:16])=[CH:13][CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 1264-HydroxybenzaldehydeHCID 784Hydrogen PeroxideHCID 11776TriphenylphosphineHCID 30305411-(Piperidin-1-yl)ethanolHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 111838924-(2-(Piperidin-1-yl)ethoxy)benzaldehydeYield 35%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A 1 L 3-neck round bottom flask was charged with anhydrous THF (200 mL), 1-piperidinylethanol (14.9 g, 15.27 mL, 0.115 mol), 4-hydroxybenzaldehyde (14.16 g, 0.116 mol), and triphenylphosphine (31,21 g, 0.119 mol) under a nitrogen atmosphere. The above mixture was stirred and diethylazodicarboxylate (DEAD; 22.6 g, 20.4 mL, 0.130 mol) in anhydrous THF (25 mL) was added dropwise over 15 min during which time the temperature was carefully monitored and not allowed to exceed 60° C. The reaction was stirred overnight at ambient temperature and then worked up by the addition of 10 mL 30% hydrogen peroxide and extraction of by ethyl ether. The organic layer was washed eight times with water, dried over anhydrous sodium sulfate, and concentrated to an oil. The oil was purified by chromatography over silica gel using a Waters LC2000 instrument. The elution solvent employed a gradient system beginning with 100% methylene chloride and ramping to 9:1 methylene chloride:methanol over 50 min at a flow rate of 150 mL/min. Concentration of appropriate fractions provided 9.2 g (35%) of the desired product as a pale brown oil.

Workup

  1. customto exceed 60° C
  2. stirringThe reaction was stirred overnight at ambient temperature
  3. washThe organic layer was washed eight times with water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated to an oil
  6. customThe oil was purified by chromatography over silica gel using a Waters LC2000 instrument

Sources & evidence

ORD record
ord-13d0685bee0a4c4a9043c67ced2fa53b
Source dataset
uspto-grants-1999_11
Patent number
US05994370

Reaction notes

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