Water → 1,1-Dimethylethyl 1-ethyl-5-oxo-prolinate

Participants

Reaction Steps

1,1-dimethylethyl 5-oxo-L-prolinate (2.7 g, 12 mmol, prepared as described in Synth. Comm., 2005, 35(8), 1129) was added to a suspension of sodium hydride (0.428 g (60% suspension in oil), 10.7 mmol) in tetrahydrofuran (6 ml) and the mixture was stirred at room temperature for 5 minutes. Ethyl iodide (1.67 g, 10.7 mmol) was then added and the mixture was heated at 40° C. for 2 hrs. A further quantity of sodium hydride (0.24 g) was added and stirring continued overnight at room temperature. An additional quantity of ethyl iodide (0.86 ml) was added to the mixture at this stage and the mixture was left to stand at room temperature over the weekend. Water (˜10 ml) was added to the mixture and this was stirred for 15 minutes. The tetrahydrofuran was evaporated and the remaining aqueous layer was extracted with dichloromethane (2×50 ml) and a 3:1 mixture of chloroform and isopropanol (50 ml). The combined organic layers were filtered through a hydrophobic frit and evaporated to give a yellow oil. Toluene was added to the mixture and then evaporated to a yellow oil once more. This material was purified by automated silica flash-column chromatography (Biotage SP4), eluting with a 15-100% gradient of ethyl acetate in hexane, to give pure 1,1-dimethylethyl 1-ethyl-5-oxo-prolinate.

Provenance & Evidence