Ethyl Acetate → 3-Chloro-4-(3-fluorobenzyloxy)aniline

HRID 222020Notes

Reaction equation

HRID 222020 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[O:11][C:12](=O)[C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1.CCOC(C)=O>C(O)(=O)C.[Fe]>[Cl:1][C:2]1[CH:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 8881677HCID 8881677, compound

Product 1

HCID 70592633-Chloro-4-(3-fluorobenzyloxy)aniline

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Procedure

2-chloro-1-(3-fluoro-benzoyloxy)-4-nitro-benzene (10 g, 35.5 mmol) was suspended in 50 mL acetic acid and 150 mL EtOAc in a 500 mL flask. Iron (9.9 g (177.5 mmol) was added to this suspension, and the mixture stirred at rt overnight. The reaction mixture was filtered through a thin pad of Celite®. The filtrate was concentrated in vacuo and neutralized with saturated Na2CO3 aq solution, followed by EtOAc extraction. The organic layer was washed with brine, dried over Na2SO4, and concentrated in vacuo. The resulting crude material was purified by flash chromatography eluting with 15% EtOAc/hexanes yielding 3-Chloro-4-(3-fluoro-benzyloxy)-phenylamine as a brown solid [8.5 g, 95%, TLC Rf=0.4, 30% EtOAc/HEX. (3:7)]. 1H-NMR (DMSO-d6) δ 4.94 (s, 2H), 5.00 (s, 2H), 6.40 (dd, 1H), 6.60 (s, 1H), 6.87 (d, 1H), 7.10-7.18 (m, 1H), 7.20-7.28 (m, 2H), 7.37-7.44 (m, 1H).

Workup

  1. filtrationThe reaction mixture was filtered through a thin pad of Celite®
  2. concentrationThe filtrate was concentrated in vacuo
  3. extractionfollowed by EtOAc extraction
  4. washThe organic layer was washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by flash chromatography
  8. washeluting with 15% EtOAc/hexanes

Sources & evidence

ORD record
ord-d0c05c23af97451f8307f2ba2b08cb13
Source dataset
uspto-grants-2012_06
Patent number
US08207172B2

Reaction notes

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