Dichloromethane → 2-Amino-4-fluoro-5-iodobenzoic acid

HRID 458092Notes

Reaction equation

HRID 458092 reaction equation
ClCCl.[NH2:4][C:5]1[CH:13]=[C:12]([F:14])[CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=[O:8].C(=O)([O-])O.[Na+].[I:20](Cl)(=O)=O.I(Cl)(=O)=O.C([N+](C)(C)C)C1C=CC=CC=1>CO>[NH2:4][C:5]1[CH:13]=[C:12]([F:14])[C:11]([I:20])=[CH:10][C:6]=1[C:7]([OH:9])=[O:8]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 27249674-Fluoroanthranilic acidHCID 56924451Trimethylbenzylammonium Dichloroiodate

Product 1

HCID 219521462-Amino-4-fluoro-5-iodobenzoic acidYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a vigorously stirred solution of dichloromethane (700 ml), methanol (320 ml), and 2-amino-4-fluoro-benzoic acid (33.35 grams, 215 mmoles) was added solid sodium hydrogencarbonate (110 grams, 1.31 moles) followed by portion addition of benzyltrimethyl ammonium dichloroiodate (82.5 grams, 237 mmoles). The mixture was allowed to stir for 48 hours. The mixture was filtered to remove the insolubles. The remaining solid residue was washed with 200 ml of dichloromethane. The filtrate was concentrated and redissolved in a one to one mixture of ethyl acetate (1 liter) and a 0.2 N solution of sodium hydroxide (1 liter), added to a 2 liter separatory funnel and extracted. The organic layer was washed with an additional 200 ml of water. The aqueous layers were combined and acidified with 2N hydrochloric acid. The resulting precipitate was collected by suction filtration, washed with water and dried under vacuum at 60° C. to yield 46.5 grams (77%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ: 8.04 (d, 1H), 7.1 (s, broad, 2H), 6.63 (d, 1H). ESI-MS m/z 280 (M−1).

Workup

  1. filtrationThe mixture was filtered
  2. customto remove the insolubles
  3. washThe remaining solid residue was washed with 200 ml of dichloromethane
  4. concentrationThe filtrate was concentrated
  5. dissolutionredissolved in a one to one mixture of ethyl acetate (1 liter)
  6. additiona 0.2 N solution of sodium hydroxide (1 liter), added to a 2 liter separatory funnel
  7. extractionextracted
  8. washThe organic layer was washed with an additional 200 ml of water
  9. filtrationThe resulting precipitate was collected by suction filtration
  10. washwashed with water
  11. customdried under vacuum at 60° C.

Sources & evidence

ORD record
ord-400955cd04eb4921936eff7c409fa3b8
Source dataset
uspto-grants-2007_03
Patent number
US07189734B2

Reaction notes

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