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

HRID 2290518Notes

Reaction equation

HRID 2290518 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
-35 °C

Procedure

To 40.92 g (310 mmol) of malonic acid half ethyl ester in 700 ml of dry tetrahydrofuran at -35° was added a stream of n-butyllithium until one equivalent was delivered. The mixture was maintained at -15° to -30° during addition, and was warmed to -5° when 10 mg of bipyridyl was added. The remainder of the n-butyllithium was added at this temperature until the indicator turned pink. A total of 282 ml of 2.2 N n-butyllithium was added. The mixture was recooled to -78° C. and a solution of 2,3,4,5-tetrafluorobenzoyl chloride was added in 100 ml of dry tetrahydrofuran keeping the temperature constant. The reaction mixture was stirred 45 minutes after the complete 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 bicarbonate 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-oxobenzenepropanoic acid, ethyl ester, mp 63°-65° C.

Workup

  1. temperatureThe mixture was maintained at -15° to -30° during addition
  2. additionwas added
  3. customwas recooled to -78° 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 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-b225bbf50342483daa42efdbb70b3660
Source dataset
uspto-grants-1986_10
Patent number
US04617308

Reaction notes

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