Propanal → Ethyl 2,2-difluoro-3-hydroxypentanoate

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Reaction Steps

Into a 2-L glass flask with a dropping funnel and a condenser, 70.6 g (1.08 mol/1.1 eq) of activated zinc metal and 300 mL of tetrahydrofuran (THF, dehydrated) were added. An ethyl bromodifluoroacetate/THF solution (prepared by dissolving 200 g (0.985 mol) of ethyl bromodifluoroacetate into 80 mL of THF (dehydrated)) and a propionaldehyde/THF solution (prepared by dissolving 58.7 g (1.01 mol/1.0 eq) of propionaldehyde in 80 mL of THF (dehydrated)) were simultaneously dropped into the glass flask. The resulting solution was stirred for 2 hours at room temperature. The completion of the reaction was confirmed by gas chromatography. After that, the solution was separated into an organic layer and an aqueous layer with the addition of water and diisopropyl ether. The thus-obtained organic layer was washed with diluted hydrochloric acid and with water, dried, concentrated under a reduced pressure, and then, distillated under a reduced pressure. With this, 110 g of 2,2-difluoro-3-hydroxy-pentanoic acid ethyl ester was obtained as a light-brown oily substance (yield: 60%, purity: 98%).

Provenance & Evidence