Ammonium Chloride → 4,5-Difluoro-N6-(2-fluoro-4-iodo-phenyl)-benzofuran-6,7-diamine

HRID 1261396Notes

Reaction equation

HRID 1261396 reaction equation
[F:1][C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[C:5]([N+:11]([O-])=O)=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=2[F:22])[C:3]=1[F:23].[NH4+].[Cl-]>C1COCC1.O.[Zn]>[F:1][C:2]1[C:7]2[CH:8]=[CH:9][O:10][C:6]=2[C:5]([NH2:11])=[C:4]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=2[F:22])[C:3]=1[F:23]

Participants

6

Reactant 2

HCID 25517Ammonium Chloride2×HCID 67235416(4,5-Difluoro-7-nitro-benzofuran-6-yl)-(2-fluoro-4-iodo-phenyl)-amine

Product 1

HCID 683132694,5-Difluoro-N6-(2-fluoro-4-iodo-phenyl)-benzofuran-6,7-diamine

Reagents, catalysts & solvents 3

HCID 23994ZincCatalyst3×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

For scale up synthesis, a solution of (4,5-difluoro-7-nitro-benzofuran-6-yl)-(2-fluoro-4-iodo-phenyl)-amine (165 g) and NH4Cl in 2.5 L of THF and 2.5 L of water was cooled to between 0° C. and 5° C. Zinc dust was added (portionwise) at a temperature of less than 25° C. (exothermic during first half of addition) over 30 minutes. The addition of zinc dust resulted in a color change from yellow to dark purple and to pale yellow. Complete conversion was achieved with the addition of NH4Cl (50 g) and zinc (60 g), followed by vigorous stirring for 20 minutes and a further 1.5 hours. Purity was 89.5%. The suspension was filtered and rinsed with 1 L of water and 1.5 L of THF. The combined solution was concentrated to remove THF (87.7% purity). 3 L of EA was added with stirring for 30 minutes. The layers were separated; the EA layer was washed with 2 L of water twice and then dried of MgSO4. The EA was filtered and concentrated to dryness. The crude was used in the next step without further purification. 1H NMR (CDCl3, 400 MHz): δ 8.06 (d, 1H), 7.46 (dd, 1H), 7.40 (bs, 1H), 7.19 (d, 1H), 7.07 (d, 1H), 6.11 (t; 1H); 5.33 (bs, 1H).

Workup

  1. customFor scale up synthesis
  2. additionat a temperature of less than 25° C. (exothermic during first half of addition) over 30 minutes
  3. customresulted in a color change from yellow to dark purple and to pale yellow
  4. filtrationThe suspension was filtered
  5. washrinsed with 1 L of water and 1.5 L of THF
  6. concentrationThe combined solution was concentrated
  7. customto remove THF (87.7% purity)
  8. addition3 L of EA was added
  9. stirringwith stirring for 30 minutes
  10. customThe layers were separated
  11. washthe EA layer was washed with 2 L of water twice
  12. dry with materialdried of MgSO4
  13. filtrationThe EA was filtered
  14. concentrationconcentrated to dryness
  15. customThe crude was used in the next step without further purification

Sources & evidence

ORD record
ord-d92e83f509154db6996ffb9b9cc665e5
Source dataset
uspto-grants-2013_06
Patent number
US08470878B2

Reaction notes

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