[C:1]([O:8][CH2:9][CH3:10])(=[O:7])[C:2]([O:4]CC)=O.[O:11]1[CH2:15][CH2:14][CH2:13][CH2:12]1.[NH4+].[Cl-].O.[C:19](OCC)(=[O:21])[CH3:20]>>[O:21]1[CH2:19][CH2:20][O:11][CH:15]1[CH2:14][CH2:13][CH2:12][C:2](=[O:4])[C:1]([O:8][CH2:9][CH3:10])=[O:7]A 1 L 3-necked round bottom flask was equipped with a nitrogen line, overhead stirrer, and thermocouple. Under a nitrogen atmosphere, the flask was charged with diethyl oxalate (73.85 g) and tetrahydrofuran (250 mL). The solution was cooled to -60° C., and the liquid portion of the Grignard reagent was added to the cooled diethyl oxalate solution via cannula to maintain the temperature below -55° C. The Grignard preparation flask was washed with tetrahydrofuran (3×20 mL), and the resulting wash was added via cannula. The addition was complete after 1.5 hours, and the reaction was stirred for about 2 hours at -60° C. to -55° C. The cold reaction mixture was immediately poured into a mixture consisting of NH4Cl (32.1 g), water (100 mL), ice (200 g) and ethyl acetate (300 mL). The layers were separated and the aqueous layer was extracted again with ethyl acetate (2×300 mL). The combined organic layers were dried over magnesium sulfate and concentrated to afford 87 g (79 M % yield) of 5-(1,3-dioxolan-2-yl)-2-oxo-pentanoic acid, ethyl ester as a thick liquid.
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