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

Temperature

-70 °C

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%).

1. temperatureto maintain the internal temperature below −70° C
2. washto rinse the addition funnel
3. additionadded dropwise over 47 minutes
4. temperatureto maintain the reaction temperature below −70° C
5. washto rinse the addition funnel
6. additionwas quickly added
7. temperatureto warm to 10° C. over 60 minutes
8. washThe resulting solution was washed with saturated aqueous sodium carbonate (2×450 mL) and saturated aqueous sodium chloride (1×450 mL)
9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated on a rotary evaporator
12. customThis product was purified by flash chromatography
13. washeluting with ethyl acetate:hexanes (90:10)

ORD record

ord-3689d44509c747f68e9ff09f2cf5e70a

Source dataset

uspto-grants-2001_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06313290B1