Hydrochloric Acid → Ethyl 3-(4-bromo-2,3,5,6-tetrafluorophenyl)-3-oxopropanoate

HRID 1904593Notes

Reaction equation

HRID 1904593 reaction equation
C([Li])CCC.[CH2:6]([O:8][C:9](=[O:14])[CH2:10][C:11]([O-:13])=O)[CH3:7].[Br:15][C:16]1[C:24]([F:25])=[C:23]([F:26])[C:19](C(Cl)=O)=[C:18]([F:27])[C:17]=1[F:28].Cl>O1CCCC1.N1C=CC=CC=1C1C=CC=CN=1>[Br:15][C:16]1[C:17]([F:28])=[C:18]([F:27])[C:19]([C:11]([CH2:10][C:9]([O:8][CH2:6][CH3:7])=[O:14])=[O:13])=[C:23]([F:26])[C:24]=1[F:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 27832454-Bromo-2,3,5,6-tetrafluorobenzoyl chlorideHCID 3595298Propanedioic acid, monoethyl esterHCID 178418339Butyllithium3×

Product 1

HCID 9974705Ethyl 3-(4-bromo-2,3,5,6-tetrafluorophenyl)-3-oxopropanoateYield 86.9%

Reagents, catalysts & solvents 2

HCID 14742,2'-BipyridineCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

n-Butyllithium (192 ml, 2.4M in hexane) was slowly added to a stirred solution of 30.24 g monoethylmalonate and 15 mg 2,2'-bipyridine in 500 ml tetrahydrofuran cooled to -60° to -70° C. under nitrogen. After about half of the butyllithium had been added, the temperature of the mixture was raised to -20° to -25° C. at which temperature the remainder of the butyllithium was added. The reaction mixture was then recooled to -60° to -70° C. and 33.41 g 4-bromo-2,3,5,6-tetrafluorobenzoyl chloride in 10 ml tetrahydrofuran was added. The reaction mixture was allowed to warm to room temperature, stirred overnight, and then poured into 460 ml 1M hydrochloric acid. The organic layer was separated, dried (magnesium sulfate) and concentrated. The residue was dissolved in ether, washed with aqueous potassium bicarbonate solution, dried (magnesium sulfate), concentrated and distilled to give 34.18 g ethyl 4-bromo-2,3,5,6-tetrafluorobenzoylacetate, b.p. 112°-117° C.(0.8 mm.).

Workup

  1. temperaturecooled to -60° to -70° C. under nitrogen
  2. additionwas added
  3. customwas then recooled to -60° to -70° C.
  4. customThe organic layer was separated
  5. dry with materialdried (magnesium sulfate)
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in ether
  8. washwashed with aqueous potassium bicarbonate solution
  9. dry with materialdried (magnesium sulfate)
  10. concentrationconcentrated
  11. distillationdistilled

Sources & evidence

ORD record
ord-d5d67c1bf99f4aa39c3bf2d2d717f6a3
Source dataset
uspto-grants-1989_06
Patent number
US04839355

Reaction notes

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