Dimethylformamide → [(Z)-1-aminoethylideneamino] 2-fluoro-6-iodobenzoate

HRID 1193115Notes

Reaction equation

HRID 1193115 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([I:11])[C:3]=1[C:4]([OH:6])=[O:5].C(Cl)(=O)C(Cl)=O.CN(C=O)C.O[NH:24][C:25](=[NH:27])[CH3:26]>C(Cl)Cl>[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([I:11])[C:3]=1[C:4]([O:6]/[N:24]=[C:25](\[NH2:27])/[CH3:26])=[O:5]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 27333022-Fluoro-6-iodobenzoic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 87262981[(Z)-1-aminoethylideneamino] 2-fluoro-6-iodobenzoateYield 86.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a heterogeneous mixture of 2-fluoro-6-iodobenzoic acid (1.51 g, 5.66 mmol) at 0° C. in DCM (28 mL) was added oxalyl chloride (0.635 mL, 7.36 mmol) followed by DMF (0.15 mL). Gas evolution commenced immediately and after 5 min the ice bath was removed. When gas evolution had ceased and the mixture was homogeneous an aliquot was removed and quenched with MeOH. Formation of the methyl ester was confirmed by HPLC and the mixture was concentrated in vacuo. The viscous liquid was dissolved in fresh DCM (28 mL) and treated with solid N-hydroxyacetamidine (503 mg, 6.79 mmol) in several portions followed by TEA (1.2 mL, 8.49 mmol) at 0° C. After stirring for 14 h at ambient temperature the mixture was washed with saturated aqueous NaHCO3 solution. The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. Chromatography (Hex to 100% EtOAc/Hex) afforded the desired product as a colorless oil (1.57 g, 86%). MS (ESI) mass calculated for C9H8FIN2O2, 321.96; m/z found, 323.0. 1H NMR (500 MHz, CDCl3): 7.70-7.65 (m, 1H), 7.15-7.11 (m, 2H), 4.87 (br s, 2H), 2.06 (s, 3H).

Workup

  1. customthe ice bath was removed
  2. customwas removed
  3. customquenched with MeOH
  4. concentrationthe mixture was concentrated in vacuo
  5. dissolutionThe viscous liquid was dissolved in fresh DCM (28 mL)
  6. washwas washed with saturated aqueous NaHCO3 solution
  7. dry with materialThe combined organic extracts were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ac07d14a06c84589bc88cb074e2e3fc4
Source dataset
uspto-grants-2014_03
Patent number
US08680275B2

Reaction notes

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