Methanol → Methyl 4-(allylamino)-5-amino-3-fluoro-2-(2-fluoro-4-iodophenylamino)benzoate

HRID 1373196Notes

Reaction equation

HRID 1373196 reaction equation
[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[C:8]([N+:10]([O-])=O)[C:7]([NH:13][CH2:14][CH:15]=[CH2:16])=[C:6]([F:17])[C:5]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26].[Cl-].[NH4+].CO.C(=O)(O)[O-].[Na+]>[Fe].CCCCCC.CCOC(C)=O.O1CCOCC1>[CH3:1][O:2][C:3](=[O:27])[C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([NH:13][CH2:14][CH:15]=[CH2:16])=[C:6]([F:17])[C:5]=1[NH:18][C:19]1[CH:24]=[CH:23][C:22]([I:25])=[CH:21][C:20]=1[F:26]

Participants

9

Reactant 4

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 58781109Methyl 4-(allylamino)-3-fluoro-2-(2-fluoro-4-iodophenylamino)-5-nitrobenzoate

Product 1

HCID 58781154Methyl 4-(allylamino)-5-amino-3-fluoro-2-(2-fluoro-4-iodophenylamino)benzoate

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A stirred suspension of 4-allylamino-3-fluoro-2-(2-fluoro-4-iodo-phenylamino)-5-nitro-benzoic acid methyl ester (125.0 g, 0.25 mol), ammonium chloride (300.0 g, 8.58 mol) in 1:1 v/v mixture of methanol (4.0 lit) and dioxane (4.0 lit) was heated until it became a clear solution and was added iron powder (150.0 g, 2.68 mol) under a positive stream of nitrogen gas. The reaction mixture was refluxed for 16 h (completion of reaction is confirmed by TLC-EtOAc:Hexane/3:5) and poured onto a mixture of 10 kg of crushed ice and 6.5 L of saturated sodium bicarbonate. To the mixture was added 1 kg of Celite®, stirred and the thick suspension was filtered through a Celitetbed. The Celite® bed was rinsed with water, then with ethyl acetate and ethyl acetate layer was separated. The aqueous layer was extracted with ethyl acetate (3 L) and the combined organic extracts are washed with water (3 L), brine (2 L), dried over anhydrous Na2SO4, filtered and evaporated under vacuum to give the title compound as oil (light brown color), which was used in the next step without further purification. Yield: 110 (93.55%)

Workup

  1. temperaturewas heated until it
  2. temperatureThe reaction mixture was refluxed for 16 h
  3. additionTo the mixture was added 1 kg of Celite®
  4. filtrationthe thick suspension was filtered through a Celitetbed
  5. washThe Celite® bed was rinsed with water
  6. customwith ethyl acetate and ethyl acetate layer was separated
  7. extractionThe aqueous layer was extracted with ethyl acetate (3 L)
  8. washthe combined organic extracts are washed with water (3 L), brine (2 L)
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. customevaporated under vacuum

Sources & evidence

ORD record
ord-999181f8c8424048aa82a131e0450967
Source dataset
uspto-grants-2007_01
Patent number
US07160915B2

Reaction notes

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