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

HRID 450452Notes

Reaction equation

HRID 450452 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-41bc0854d5064af6a1b60c8cab5011c6
Source dataset
uspto-grants-2013_07
Patent number
US08486951B2

Reaction notes

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