Hydrochloric Acid → diethyl 2-(2,6-difluorophenyl)malonate

HRID 1348555Notes

Reaction equation

HRID 1348555 reaction equation
[H-].[Na+].[C:3]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:4][C:5]([O-:7])=[O:6].Br[C:13]1[C:18]([F:19])=[CH:17][CH:16]=[CH:15][C:14]=1[F:20].Cl.CO[C:24](C)(C)[CH3:25]>O.O1CCOCC1>[F:20][C:14]1[CH:15]=[CH:16][CH:17]=[C:18]([F:19])[C:13]=1[CH:4]([C:5]([O:7][CH2:24][CH3:25])=[O:6])[C:3]([O:9][CH2:10][CH3:11])=[O:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 15413tert-Butyl methyl etherHCID 24758Sodium hydrideHCID 1235571-Bromo-2,6-difluorobenzeneHCID 3595298Propanedioic acid, monoethyl ester

Product 1

HCID 2782019diethyl 2-(2,6-difluorophenyl)malonate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

Into a mixture of 8.00 g of sodium hydride (60% in oil) and 100 ml of 1,4-dioxane, 32.0 g of ethyl malonate were added dropwise at 60° C. , further 14.6 g of cuprous bromide and 19.3 g of 1-bromo-2,6-difluorobenzene were added subsequently, and then refluxed for 16 hours under heating. To the reaction mixture, conc. hydrochloric acid was added under ice-cooling, and then tert-butyl methyl ether and water were added. The separated organic layer was washed with dil. hydrochloric acid and water subsequently, dried over sodium sulfate and concentrated. The residue was distilled under reduced pressure to give 16.5 g of diethyl (2,6-difluorophenyl)malonate. b.p. 107–109° C. (0.14 mmHg)

Workup

  1. additionwere added dropwise at 60° C.
  2. temperaturerefluxed for 16 hours
  3. temperatureunder heating
  4. temperaturecooling
  5. washThe separated organic layer was washed with dil. hydrochloric acid and water subsequently
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. distillationThe residue was distilled under reduced pressure

Sources & evidence

ORD record
ord-ac2f3bdbb4f14c87a2c1e4b306737d82
Source dataset
uspto-grants-2007_05
Patent number
US07211545B2

Reaction notes

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