Acetic Acid → 4-(4-amino-2-fluorophenyl)-N-methylbutanamide

HRID 1192868Notes

Reaction equation

HRID 1192868 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[CH:5]=[CH:4][C:3]=1[CH2:11][CH2:12][CH2:13][C:14]([NH:16][CH3:17])=[O:15].CC(O)=O>C(OCC)(=O)C.[Fe]>[NH2:8][C:6]1[CH:5]=[CH:4][C:3]([CH2:11][CH2:12][CH2:13][C:14]([NH:16][CH3:17])=[O:15])=[C:2]([F:1])[CH:7]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 687330104-(2-fluoro-4-nitrophenyl)-N-methylbutanamide

Product 1

HCID 687332914-(4-amino-2-fluorophenyl)-N-methylbutanamideYield 95.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
21 °C

Procedure

A solution of compound 4-(2-Fluoro-4-nitrophenyl)-N-methylbutanamide (81) (18 mg, 0.07 mmol), Fe (30 mg, 0.52 mmol) and AcOH (1 mL) in ethyl acetate (3 mL) was heated under reflux for 2 h. The reaction mixture was allowed to cool to 21° C. and then filtered. The organic layer was concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give desired 4-(4-Amino-2-fluorophenyl)-N-methylbutanamide (80) (14 mg, 86%): 1H NMR δ 6.92 (dd, 1H, J=8.3, 8.2 Hz), 6.39 (dd, 1H, J=8.3, 2.0 Hz), 6.33 (dd, 1H, J=13.3, 2.0 Hz), 5.48 (br s, 1H), 3.69 (br s, 2H), 2.79 (d, 3H, J=4.8 Hz), 2.55 (t, 2H, J=7.4 Hz) 2.16 (t, 2H, J=7.5 Hz) 1.85-1.94 (m, 2H).

Workup

  1. temperatureunder reflux for 2 h
  2. filtrationfiltered
  3. concentrationThe organic layer was concentrated
  4. customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1)

Sources & evidence

ORD record
ord-839a9d6990a24284bee3088adf33cba5
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

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