2-Fluoro-N-methyl-4-nitrobenzamide → 4-Amino-2-fluoro-N-methylbenzamide

HRID 1927369Notes

Reaction equation

HRID 1927369 reaction equation
[CH3:1][NH:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([N+:10]([O-])=O)=[CH:6][C:5]=1[F:13]>C(OCC)(=O)C.C(O)(=O)C.[Fe]>[CH3:1][NH:2][C:3](=[O:14])[C:4]1[CH:9]=[CH:8][C:7]([NH2:10])=[CH:6][C:5]=1[F:13]

Participants

5

Reactant 1

HCID 534406322-Fluoro-N-methyl-4-nitrobenzamide

Product 1

HCID 441395214-Amino-2-fluoro-N-methylbenzamideYield 94%

Reagents, catalysts & solvents 3

HCID 23925IronCatalystHCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of N-methyl-2-fluoro-4-nitrobenzamide (52a) (2.89 g, 14.6 mmol) and iron (5.04 g, 90 mmol) in ethyl acetate (40 ml) and acetic acid (40 ml) was refluxed for 1 hour. The solid particles were filtered off. The filtrate was washed with water and extracted with ethyl acetate. The organic layer was dried over MgSO4, concentrated and chromatographed (dichloromethane:acetone, 95:5) to yield N-methyl-2-fluoro-4-aminobenzamide (52b) (2.3 g, 13.7 mmol, 94%) as an off-white solid. 1H NMR (acetone-d6, 400 MHz) δ 2.86 (d, J=4.3 Hz, 3H), 5.50 (bs, 2H), 6.37 (dd, J1=14.7 Hz, J2=2.1 Hz, 1H), 6.50 (dd, J=8.5, 2.1 Hz, 1H), 7.06 (bs, 1H), 7.68 (dd, J=8.8, 8.8 Hz, 1H); 13C NMR (acetone-d6, 100 MHz) δ 25.8, 99.6 (d, J=13.8 Hz), 109.2 (d, J=12.8 Hz), 110.0 (d, J=1.6 Hz), 132.5 (d, J=4.8 Hz), 153.5 (d, J=12.6 Hz), 162.2 (d, J=242.5 Hz), 164.0 (d, J=3.1 Hz).

Workup

  1. temperaturewas refluxed for 1 hour
  2. filtrationThe solid particles were filtered off
  3. washThe filtrate was washed with water
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated
  7. customchromatographed (dichloromethane:acetone, 95:5)

Sources & evidence

ORD record
ord-c9868c8d9ff24a0b98f3f374b94d8608
Source dataset
uspto-grants-2012_05
Patent number
US08183274B2

Reaction notes

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