Ethyl Acetate → 4-Amino-2-fluoro-N-methylbenzamide

HRID 2407519Notes

Reaction equation

HRID 2407519 reaction equation
[F:1][C:2]1[CH:11]=[C:10]([N+:12]([O-])=O)[CH:9]=[CH:8][C:3]=1[C:4]([NH:6][CH3:7])=[O:5].C(OCC)(=O)C>[Fe].C(O)(=O)C>[NH2:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([NH:6][CH3:7])=[O:5])=[C:2]([F:1])[CH:11]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 534406322-Fluoro-N-methyl-4-nitrobenzamide

Product 1

HCID 441395214-Amino-2-fluoro-N-methylbenzamide

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 2-fluoro-N-methyl-4-nitro-benzamide 21 (3 g, 15.1 mmol) in co-solvent of ethyl acetate and acetic acid (12 mL+12 mL) was added iron dust (8 g, 143. mmol). The suspension was heated at reflux until the starting material disappeared in LCMS. Cooled down to 25° C. The solid was filtered off and the filtrate was diluted with ethyl acetate (50 mL). The organic phase was washed with brine (3×30 mL), dried (MgSO4) and concentrated to dryness in vacuo. The title compound 4a was obtained as an orange solid (2.5 g, 97% yield). MS: 169 (M+H)+. 1H NMR (acetone-d6, 500 MHz): δ 7.69 (1H, dd, J=8.7, 8.8 Hz), 7.15 (1H, s), 6.51 (1H, dd, J=8.6, 2.1 Hz), 6.38 (1H, dd, J=14.7, 2.1 Hz), 5.70 (1H, br s), 2.88 (3H, d, J=4.3 Hz).

Workup

  1. temperatureThe suspension was heated
  2. temperatureat reflux until the starting material
  3. filtrationThe solid was filtered off
  4. additionthe filtrate was diluted with ethyl acetate (50 mL)
  5. washThe organic phase was washed with brine (3×30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record
ord-a0ab1e41fc3e46ceaef42f52c38611d8
Source dataset
uspto-grants-2014_08
Patent number
US08809550B2

Reaction notes

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