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

HRID 868126Notes

Reaction equation

HRID 868126 reaction equation
[C:1]([OH:7])(=[O:6])[CH2:2][C:3]([OH:5])=O.[CH2:8]([Li])[CH2:9]CC.N1C=CC=CC=1C1C=CC=CN=1.[F:25][C:26]1[C:34]([F:35])=[C:33]([F:36])[C:32]([F:37])=[CH:31][C:27]=1C(Cl)=O.Cl>O1CCCC1.ClCCl.O>[F:37][C:32]1[C:33]([F:36])=[C:34]([F:35])[C:26]([F:25])=[CH:27][C:31]=1[C:3](=[O:5])[CH2:2][C:1]([O:7][CH2:8][CH3:9])=[O:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 867Malonic AcidHCID 14742,2'-BipyridineHCID 27336892,3,4,5-Tetrafluorobenzoyl chlorideHCID 178418339Butyllithium3×

Product 1

HCID 600916Ethyl 3-oxo-(2,3,4,5-tetrafluorophenyl)propanoate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-5 °C

Procedure

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° 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 2 N 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 sodium bicarbonate and then 1 N 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-tetrafluoroβ-oxo-benzenepropanoic acid, ethyl ester, mp 63°-65° C.

Workup

  1. temperatureThe mixture was maintained at -15° to -30° 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 sodium bicarbonate
  7. dry with materialThe dichloromethane was dried (magnesium sulfate)
  8. concentrationconcentrated to a solid which
  9. customwas triturated with cold pentane

Sources & evidence

ORD record
ord-77a68f82c8c940e2a5cf4746a51ee1de
Source dataset
uspto-grants-1988_10
Patent number
US04777175

Reaction notes

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