Ammonium Chloride → Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-

HRID 2060698Notes

Reaction equation

HRID 2060698 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[C:13]([F:15])[C:12]([N+:16]([O-])=O)=[CH:11][C:10]=2[F:19])[CH:5]=[CH:4][N:3]=1.[Cl-].[NH4+]>C1COCC1.CO.[Zn]>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[C:10]([F:19])=[CH:11][C:12]([NH2:16])=[C:13]([F:15])[CH:14]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 552369312-Chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine

Product 1

HCID 78358387Benzenamine, 4-[(2-chloro-4-pyridinyl)oxy]-2,5-difluoro-Yield 590.1%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 2-chloro-4-(2,5-difluoro-4-nitrophenoxy)pyridine (3.57 g, 2.1 mmol), zinc dust (8.14 g, 125 mmol) and ammonium chloride (6.66 g, 125 mmol) in THF (160 mL) and MeOH (160 ml) was stirred at RT for 2 h. The reaction mixture was filtered and the filtrate was concentrated under reduced pressure. The crude product was partitioned between EtOAc (50 ml) and a mixture of water and saturated NaHCO3 (aq) (1:1; 50 ml). The mixture was extracted with EtOAc (2×50 ml). The combined organic extracts were dried (Na2SO4) and evaporated to yield 4-(2-chloropyridin-4-yloxy)-2,5-difluoroaniline (3.18 g, 100% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.26 (d, 1H), 7.24-7.19 (m, 1H), 7.00 (s, 1H), 6.94-6.92 (m, 1H), 6.74-6.69 (m, 1H), 5.54 (brs, 2H); MS (ESI) m/z: 257.0 (M+H+).

Workup

  1. filtrationThe reaction mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe crude product was partitioned between EtOAc (50 ml)
  4. additiona mixture of water and saturated NaHCO3 (aq) (1:1; 50 ml)
  5. extractionThe mixture was extracted with EtOAc (2×50 ml)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. customevaporated

Sources & evidence

ORD record
ord-d841c67ea6ef414ea11822698949c417
Source dataset
uspto-grants-2012_10
Patent number
US08278331B2

Reaction notes

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