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

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Reaction Steps

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.

Provenance & Evidence