Tetrahydrofuran → N-(3-Aminophenyl)-2-bromobenzene-1-carboximidic acid

HRID 1484540Notes

Reaction equation

HRID 1484540 reaction equation
[Br:1][C:2]1[CH:19]=[CH:18][CH:17]=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([N+:13]([O-])=O)[CH:8]=1)=[O:5].C1COCC1.S(S([O-])=O)([O-])=O.[Na+].[Na+]>O>[NH2:13][C:9]1[CH:8]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[CH:16]=[CH:17][CH:18]=[CH:19][C:2]=2[Br:1])[CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 24489Sodium DithioniteHCID 532191HCID 532191, compound

Product 1

HCID 784673N-(3-Aminophenyl)-2-bromobenzene-1-carboximidic acidYield 66%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Bromo-N-(3-nitrophenyl)benzamide (6.89 g, 21.5 mmol) was added to a 1 L flask with stir bar and dissolved with THF (143 mL). Sodium dithionite (37.4 g, 215 mmol) (aka sodium hydrosulfite) was added to a separate flask and dissolved with water (143 mL). The resulting cloudy solution was added to the solution of substrate, and the flask was sealed and flushed with nitrogen, then stirred vigorously for 16 h with a vent line to an oil bubbler. After this time LC-MS analysis showed complete conversion to a mixture of the desired product plus its N-sulfate. To hydrolyze the sulfated material, saturated aqueous ammonium chloride (30 mL) was added, and the mixture was refluxed for 4 h. The layers were then separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organics were washed with brine, then dried over Na2SO4, filtered, and concentrated. The crude material was then dissolved with dichloromethane and ethyl acetate, leaving an insoluble gum behind. The solution was purified by column chromatography (EtOAc/hexanes gradient), to yield the title compound as a pale yellow solid (4.10 g, 66%). LRMS (ESI+) (M+H): 291.96.

Workup

  1. additionThe resulting cloudy solution was added to the solution of substrate
  2. customthe flask was sealed
  3. customflushed with nitrogen
  4. stirringstirred vigorously for 16 h with a vent line to an oil bubbler
  5. additionto a mixture of the desired product plus its N-sulfate
  6. additionwas added
  7. temperaturethe mixture was refluxed for 4 h
  8. customThe layers were then separated
  9. extractionthe aqueous layer was extracted twice with ethyl acetate
  10. washThe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. dissolutionThe crude material was then dissolved with dichloromethane and ethyl acetate
  15. customleaving an insoluble gum behind
  16. customThe solution was purified by column chromatography (EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-fc634abbc3aa42939648830d2cd10aad
Source dataset
uspto-grants-2016_08
Patent number
US09422262B2

Reaction notes

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