2305-25-1

123-72-8

105-36-2

2305-25-1

GENERAL STEPS: THF (200 mL) was added to a 500 mL round-bottomed flask pre-dried in an oven equipped with a 30 cm long condenser and kept open to the atmosphere.THF was used directly without further drying or purification. Subsequently, it was heated to reflux temperature (66°C) on a sand bath and the solvent was rapidly stirred using a magnetic stir bar. The condenser was temporarily raised and 6.5 g (0.1 mol, 2 eq.) of ZnO particles were added to the hot solvent. Next, n-butyraldehyde (0.1 mol) and ethyl bromoacetate (0.2 mol, 2 eq.) were added to the reaction mixture. The condenser was immediately reconnected to the round-bottom flask, at which point rapid boiling was observed. After allowing the reaction to reflux rapidly for 1 min, the reaction vessel was removed from the heat source and cooled to room temperature. For all substrates, the reaction was monitored by TLC (eluent: hexane-EtOAc, 80:20) within 20 minutes to confirm completion. Excess THF was removed under vacuum, and the brown oil obtained was dissolved in hexane and the reaction quenched with H2O to form a yellow precipitate. After filtering the mixture, the hexane layer was washed sequentially with H2O (100 mL), 1M HCl (2 × 50 mL), H2O (100 mL) and brine (50 mL), and then dried with Na2SO4. Finally, hexane was removed under vacuum to afford the target product ethyl 3-hydroxyhexanoate in 86% to 95% yield (see Table 1).