Hydrochloric Acid → Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

Temperature

-5 °C

To 40.92 g (310 mmol) of malonic acid half ethyl ester in 700 ml of dry tetrahydrofuran at -35° C. was added a stream of n-butyllithium until one equivalent was delivered. The mixture was maintained at -15° to -30° C. during the addition, then warmed to -5° C. treated with 10 mg of bipyridyl. The remainder of the n-butyllithium was added at this temperature until the indicator turned pink. A total of 282 ml of 2.2N n-butyllithium was added. The mixture was recooled to -78° C. and a solution of 2,3,4,5-tetrafluorobenzoyl chloride in 100 ml of dry tetrahydrofuran was added keeping the temperature constant. The reaction mixture was stirred for 45 minutes after the acid chloride addition. It was warmed to -35° C. and poured into 155 ml of 2N hydrochloric acid. To this mixture was added one liter of water and 1.5 liters of dichloromethane. The aqueous phase was separated and extracted with an additional 1.5 liters of dichloromethane. The combined organic phases were washed with 50% saturated sodium bicarbonated and then 1N hydrochloric acid. The dichloromethane was dried (magnesium sulfate) and concentrated to a solid which was triturated with cold pentane to give 37.8 g of 2,3,4,5-tetrafluoro-β-oxo-benzenepropanoic acid, ethyl ester, mp 63°-65° C.

1. temperatureThe mixture was maintained at -15° to -30° C. during the addition
2. customwas recooled to -78° C.
3. temperatureIt was warmed to -35° C.
4. customThe aqueous phase was separated
5. extractionextracted with an additional 1.5 liters of dichloromethane
6. washThe combined organic phases were washed with 50% saturated sodium
7. dry with materialThe dichloromethane was dried (magnesium sulfate)
8. concentrationconcentrated to a solid which
9. customwas triturated with cold pentane

ORD record

ord-1c248079b6d44d62a8c9228e87a1ea54

Source dataset

uspto-grants-1987_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04663457