2-[(2-Chloro-4-nitrophenoxy)methyl]-6-methylpyridine → 3-Chloro-4-[(6-methylpyridin-2-yl)methoxy]aniline

HRID 222036Notes

Reaction equation

HRID 222036 reaction equation
[Cl:1][C:2]1[CH:16]=[C:15]([N+:17]([O-])=O)[CH:14]=[CH:13][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=1>C(O)(=O)C.[Fe]>[Cl:1][C:2]1[CH:16]=[C:15]([CH:14]=[CH:13][C:3]=1[O:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([CH3:12])[N:7]=1)[NH2:17]

Participants

4

Reactant 1

HCID 668773902-[(2-Chloro-4-nitrophenoxy)methyl]-6-methylpyridine

Product 1

HCID 220552383-Chloro-4-[(6-methylpyridin-2-yl)methoxy]anilineYield 88.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

2-[(2-chloro-4-nitrophenoxy)methyl]-6-methylpyridine (4.87 g, 17.5 mmol) and iron powder (4.87 g, 87.4 mmol) were mixed in 150 mL acetic acid, and were stirred at rt overnight. The reaction mixture was filtered through a pad of Celite®, and washed with EtOAc. The filtrate was concentrated in vacuo and neutralized with saturated Na2CO3 solution. The contents were extracted with EtOAc (5×300 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The resulting crude material was triturated with Hex/EtOAc (2:1) to afford 3-chloro-4-[(6-methylpyridin-2-yl)methoxy]aniline (3.84 g, 88%) as a white solid. 1H-NMR (DMSO) δ 7.70 (dd, 1H), 7.31 (d, 1H), 7.17 (d, 1H), 6.88 (d, 1H), 6.65 (d, 1H), 6.44 (dd, 1H), 5.01 (s, 2H), 4.93 (s, 2H), 2.46 (s, 3H); LCMS RT=0.25 min; [M+H]+=249.2.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite®
  2. washwashed with EtOAc
  3. concentrationThe filtrate was concentrated in vacuo
  4. extractionThe contents were extracted with EtOAc (5×300 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe resulting crude material was triturated with Hex/EtOAc (2:1)

Sources & evidence

ORD record
ord-c1e1ad8661e743c0b5e9fa4b91a3d4e5
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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