Nitrogen → Ethyl 2-hydroxypent-4-ynoate

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Reaction Steps

Propargyl bromide (˜10 g) was added under a blanket of N2 to a 3-L round bottom flask containing 350 mL anhydrous THF and Zn (230 g, 3.5 mol). The mixture was stirred at room temperature for 30 min and then cooled in an ice bath. A toluene solution of ethyl glyoxylate (51 wt %, determined by NMR, 473 g, 2.36 mol) and a toluene solution of propargyl bromide (80 wt %, 352 g, 2.36 mol) were combined in 500 mL dry THF and 700 mL dry ether. This mixture was then added dropwise to the stirred slurry. After the addition was complete, the mixture was stirred at 0° C. overnight. The reaction mixture was then poured into a 4-L Erlenmeyer flask containing 1 L of ice-cold 3M HCl. After separation of the organic layer, the aqueous layer was extracted with ether (3×300 mL) and the combined organic layers were dried over MgSO4. Filtration and removal of the solvents by rotary evaporation gave a dark blue oil, which was purified by column chromatography using silica gel with EtOAc/hexanes (30/70) as the eluent. Vacuum distillation of the resulting material (50-55° C./100 mTorr) gave the ester 2 as a colorless oil (170 g, 51%). 1H NMR δ 4.25 (m, 3H), 3.11 (d, 1H, J=6.4 Hz), 2.65 (m, 2H), 2.03 (t, 1H, J=2.7 Hz), 1.28 (t, 3H, J=7.2 Hz). 13C NMR δ 172.99, 78.53, 71.25, 68.64, 62.11, 24.81, 14.13.

Provenance & Evidence