Acetic Acid → Ethyl 4-(4-chloro-2-nitrophenyl)-4-hydroxy-2-butynoate

Participants

Reaction Conditions

Reaction Steps

To a cooled (−78° C.) solution of ethyl propiolate (8.96 mL, 88.4 mmol) in THF (100 mL) was added n-butyllithium (37.5 mL of 2.37M solution in hexane, 88.9 mmol) dropwise over 70 minutes so as to maintain the internal temperature below −70° C. Additional THF (5 mL) was used to rinse the addition funnel. A solution of 4-chloro-2-nitrobenzaldehyde (14.88 g, 80.2 mmol) in THF (30 mL) was transferred to the addition funnel and added dropwise over 47 minutes to maintain the reaction temperature below −70° C. Additional THF (5 mL) was used to rinse the addition funnel. The solution was stirred for 90 minutes at −70° C. and was then warmed to −60° C. glacial acetic acid (18.3 mL, 316 mmol) was quickly added. The solution was allowed to warm to 10° C. over 60 minutes and poured into diethyl ether (900 mL). The resulting solution was washed with saturated aqueous sodium carbonate (2×450 mL) and saturated aqueous sodium chloride (1×450 mL). The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated on a rotary evaporator. This product was purified by flash chromatography eluting with ethyl acetate:hexanes (90:10) to give the title compound as red oil (14.73 g, 64.8%).

Provenance & Evidence