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

HRID 1292962Notes

Reaction equation

HRID 1292962 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.C(OCC)(=O)C>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)aniline

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

2-(2-chloro-4-nitro-phenoxymethyl)-pyridine (8 g, 30.2 mmol, 1 eq) and 8.44 g iron (151.1 mmol, 5 eq) were mixed in 100 mL acetic acid and 50 mL ethyl acetate and were stirred at rt overnight. The reaction mixture was filtered through celite pad. The filtrate was concentrated in vacuo and neutralized with sat. Na2CO3 solution. The solution was extracted with ethyl acetate and the organic layer was washed with brine and concentrated in vacuo. The resulting crude material was purified by flash chromatography eluting with 30% ethyl acetate/hexane yielding 3.2 g of 3-chloro-4-(pyridin-2-ylmethoxy)-phenylamine as a white solid (52%). 1H-NMR (CDCl3) 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 celite pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. extractionThe solution was extracted with ethyl acetate
  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 30% ethyl acetate/hexane yielding 3.2 g of 3-chloro-4-(pyridin-2-ylmethoxy)-phenylamine as a white solid (52%)

Sources & evidence

ORD record
ord-decf9c34981d4b36b098bed95fe56366
Source dataset
uspto-grants-2007_07
Patent number
US07238701B2

Reaction notes

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