Diisopropylamine → 3-(2,4-Difluorophenyl)-2-propynoic acid

HRID 1594004Notes

Reaction equation

HRID 1594004 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1I.[C:10]([OH:14])(=[O:13])[C:11]#[CH:12].C(NC(C)C)(C)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:12]#[C:11][C:10]([OH:14])=[O:13]

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 10110Propiolic AcidHCID 1375192,4-Difluoro-1-iodobenzene

Product 1

HCID 636407873-(2,4-Difluorophenyl)-2-propynoic acidYield 85.3%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

4.95 ml (41.4 mmol) of 2,4-difluoroiodobenzene and 2.56 ml (41.4 mmol) of propiolic acid were dissolved in DMF (16 ml). Following cooling of the reaction medium to 0° C. (ice-water bath), 578 mg (0.83 mmol) of Pd(PPh3)2Cl2 and 308 mg (1.66 mmol) of Cul were added. The reaction solution was then cooled to −10° C. (ice methanol bath) and 14.5 ml (103.4 mmol) of diisopropylamine were added dropwise at this temperature. The cooling bath was then removed and the reaction mixture was stirred a further 16 h after RT had been re-established. The reaction solution was then diluted with EA and washed successively with a 2N HCl solution and a satd aq. NaCl solution. Following drying over MgSO4, filtration, and removal of solvent in vacuo, the residue was boiled with hexane and filtered after cooling to RT. The residue was dissolved in diethyl ether at 30° C. and filtered at this temperature. By removal of solvent in vacuo there were obtained from the filtrate 6.43 g (35.3 mmol, 85%) of (2,4-difluorophenyl)propiolic acid.

Workup

  1. additionwere added
  2. additionwere added dropwise at this temperature
  3. customThe cooling bath was then removed
  4. additionThe reaction solution was then diluted with EA
  5. washwashed successively with a 2N HCl solution
  6. dry with materialFollowing drying over MgSO4, filtration, and removal of solvent in vacuo
  7. filtrationfiltered
  8. temperatureafter cooling to RT
  9. dissolutionThe residue was dissolved in diethyl ether at 30° C.
  10. filtrationfiltered at this temperature
  11. customBy removal of solvent in vacuo

Sources & evidence

ORD record
ord-263518bedeb34e22b8bd9169c2cd241e
Source dataset
uspto-grants-2007_11
Patent number
US07300939B2

Reaction notes

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