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

HRID 2273931Notes

Reaction equation

HRID 2273931 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-dc9825f24b35431a9248185fdaa8fac1
Source dataset
uspto-grants-2015_09
Patent number
US09126941B2

Reaction notes

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