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

Participants

Reaction Conditions

Reaction Steps

1-(Thiophen-2-yl)propan-1-one oxime (6.3 g, 40.6 mmol) was dissolved in 100 mL of THF and cooled to 0° C. LDA solution (46.7 mL, 93.5 mmol, 2M in heptane/THF/ethyl benzene) was added dropwise, and the reaction mixture was stirred at 0° C. for 1 hour and then warmed to room temperature. The mixture was then transferred to an addition funnel and added dropwise to a flask containing a pre-cooled mixture of diethyl oxalate (27.6 mL, 203 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. The organic layer was separated and the aqueous layer was extracted with EtOAc. The aqueous layer was then neutralized with solid sodium bicarbonate and extracted further with CH2Cl2. The organic layers were combined, dried over MgSO4 and concentrated. The crude oil was purified by chromatography (0-20% EtOAc/hexanes) to give 7.7 g of the title compound. MS: (+) m/z 256.33 (M+1).

Provenance & Evidence