Ethyl Acetate → 3-Chloro-4-(2-pyridylmethoxy)aniline

HRID 1887403Notes

Reaction equation

HRID 1887403 reaction equation
[Cl:1][C:2]1[CH:15]=[C:14]([N+:16]([O-])=O)[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.CCOC(C)=O>C(O)(=O)C.[Fe]>[Cl:1][C:2]1[CH:15]=[C:14]([NH2:16])[CH:13]=[CH:12][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 174694332-((2-Chloro-4-nitrophenoxy)methyl)pyridine

Product 1

HCID 167812123-Chloro-4-(2-pyridylmethoxy)anilineYield 52%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8 g, 30.2 mmol, 1 equiv) and iron (8.44 g, 151.1 mmol, 5 equiv) were mixed in acetic acid (100 mL) and EtOAc (50 mL) and were stirred at rt overnight. The reaction mixture was filtered through a pad of Celite®. The filtrate was concentrated in vacuo and neutralized with saturated Na2CO3 solution. The solution was extracted with EtOAc and the organic layer was washed with brine and concentrated in vacuo. The resulting crude material was purified by flash chromatography eluting with EtOAc/hexane (3:7) to give 3-Chloro-4-(pyridin-2-ylmethoxy)-phenylamine (3.2 g, 52%) as a white solid. 1H-NMR (CDCl3-d) δ 5.18 (s, 2H), 6.50 (dd, 1H), 6.76 (d, 1H), 6.80 (d, 1H), 7.22 (m, 1H), 7.64 (d, 1H), 7.73 (td, 1H), 8.55 (m, 1H); LCMS RT=0.89 min, [M+H]+=235.1.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. concentrationThe filtrate was concentrated in vacuo
  3. extractionThe solution was extracted with EtOAc
  4. washthe organic layer was washed with brine
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by flash chromatography
  7. washeluting with EtOAc/hexane (3:7)

Sources & evidence

ORD record
ord-6e461adccdeb48c483223dc9397d3c10
Source dataset
uspto-grants-2013_08
Patent number
US08501755B2

Reaction notes

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