Picolinic acid → Diethyl (3-fluorophenyl)propanedioate

HRID 627530Notes

Reaction equation

HRID 627530 reaction equation
N1C=CC=[CH:3][C:2]=1C(O)=O.C([O-])([O-])=O.[Cs+].[Cs+].C([C:18]([CH2:25][CH3:26])([C:22]([O-:24])=[O:23])[C:19]([O-:21])=[O:20])C.[F:27][C:28]1[CH:29]=[C:30](I)C=C[CH:33]=1.[NH4+].[Cl-].O1CCO[CH2:39][CH2:38]1>[Cu]I>[F:27][C:28]1[CH:33]=[C:25]([CH:18]([C:22]([O:24][CH2:38][CH3:39])=[O:23])[C:19]([O:21][CH2:2][CH3:3])=[O:20])[CH:26]=[CH:30][CH:29]=1

Participants

8

Reactant 6

HCID 1018Picolinic acidHCID 10796Cesium carbonateHCID 25517Ammonium ChlorideHCID 312751,4-DioxaneHCID 707251-Fluoro-3-iodobenzeneHCID 69515632,2-Diethylpropanedioate

Product 1

HCID 12965551Diethyl (3-fluorophenyl)propanedioate

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Procedure

A round bottom flask was charged with copper (I) iodide (571 mg, 3.0 mmol), 2-picolinic acid (739 mg, 6.0 mmol), and Cs2CO3 (58.6 g, 180 mmol). The flask was evacuated and re-filled with argon (3 times). 1,4-dioxane (60 mL), diethylmalonate (18.2 mL, 120 mmol), and 3-fluoroiodobenzene (7.05 mL, 60 mmol) were then added in sequence. The resulting yellow suspension was stirred at room temperature overnight. To the mixture was added sat aqueous NH4Cl and the mixture was extracted with EtOAc (3×). The organic phase was washed once with water. The organic phase was dried (Na2SO4), filtered, and concentrated to yield the crude title compound as a colorless liquid, which was used without further purification.

Workup

  1. customThe flask was evacuated
  2. additionre-filled with argon (3 times)
  3. additionTo the mixture was added
  4. extractionthe mixture was extracted with EtOAc (3×)
  5. washThe organic phase was washed once with water
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-fa2203b762544985a29d97c55c00c49b
Source dataset
uspto-grants-2016_04
Patent number
US09309222B2

Reaction notes

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