Iodine → 4-Chloro-2-fluoro-6-iodobenzoic acid

HRID 596054

Reaction equation

HRID 596054 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1.C(O)(=O)C.C(O)(=O)C.[I:20]C1C=CC=CC=1.II.CN(C=O)C>CCOC(C)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:1][C:2]1[CH:10]=[C:9]([I:20])[C:5]([C:6]([OH:8])=[O:7])=[C:4]([F:11])[CH:3]=1

Participants

7

Reactant 4

HCID 807IodineHCID 6228DimethylformamideHCID 991524-Chloro-2-fluorobenzoic acid2×HCID 12217721Iodo benzene diacetate

Product 1

HCID 1180459354-Chloro-2-fluoro-6-iodobenzoic acid

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a 250 mL flask were added 4-chloro-2-fluorobenzoic acid (4 g, 22.92 mmol), Pd(OAc)2 (0.257 g, 1.146 mmol), iodobenzene diacetate (8.12 g, 25.2 mmol), iodine (6.40 g, 25.2 mmol) and DMF (60 mL). The solution was heated under a nitrogen atmosphere at 100° C. for 20 h. LCMS showed about half of 4-chloro-2-fluorobenzoic acid was converted to the product (LCMS retention time 0.98 min, no MH+ peak). After cooling to room temperature, the solution was diluted with EtOAc and washed three times with 1 N HCl. The aqueous layers were combined and extracted once with EtOAc. The organic layers were combined, dried over Na2SO4 and concentrated to give a dark brown oil (16.4 g, 42% pure), which was taken to the next step without purification.

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed three times with 1 N HCl
  3. extractionextracted once with EtOAc
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customto give a dark brown oil (16.4 g, 42% pure), which
  7. customwas taken to the next step without purification

Sources & evidence

ORD record
ord-3f19965fe351414d9c0e744a7d758022
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Linked notes

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