Diethyl Oxalate → Ethyl 4-(hydroxyimino)-3-methyl-2-oxo-4-(pyridin-4-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

1-(Pyridin-4-yl)propan-1-one oxime (5.3 g, 35.3 mmol) was dissolved in 120 mL of THF and cooled to 0° C. LDA solution (41 mL, 81.3 mmol, 2M in heptane/THF/ethyl benzene) was added dropwise, and the reaction mixture was stirred at 0° C. for 1.5 hour and then warmed to room temperature. The mixture was then transferred to a syringe and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (24 mL, 177 mmol) and THF (100 mL) at 0° C. After the addition was complete, the reaction mixture was stirred at room temperature for 18 hours. The mixture was cooled in an ice bath and quenched with 150 mL of 10% hydrochloric acid. EtOAc (150 mL) was added and solid NaHCO3 was added with vigorous stirring the aqueous layer was basic (pH>8). The aqueous layer was extracted with additional EtOAc and the combined organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (10-60% EtOAc/hexanes) to give 5.3 g of the title compound. MS: (+) m/z 251.43 (M+1).

Provenance & Evidence