Methylamine → 2-Fluoro-N-methyl-4-nitrobenzamide

HRID 2273930Notes

Reaction equation

HRID 2273930 reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:7]=1[C:8](O)=[O:9].[CH3:18][NH2:19]>CN(C=O)C>[CH3:18][NH:19][C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:13]([N+:15]([O-:17])=[O:16])=[CH:14][C:6]=1[F:5]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 24386Thionyl ChlorideHCID 3026792-Fluoro-4-nitrobenzoic acid

Product 1

HCID 534406322-Fluoro-N-methyl-4-nitrobenzamideYield 91%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-5 °C

Procedure

Thionyl chloride (2.38 g, 20 mmol) was added slowly to a solution of 2-fluoro-4-nitrobenzoic acid (2.97 g, 16 mmol) in DMF (50 ml) cooled at −5° C. The mixture was stirred for an additional 1 hour at −5° C. Methylamine (0.62 g, 20 mmol; freshly distilled from its 40% aqueous solution) was added to the reaction medium. The second mixture was stirred for an additional 1 hour. Ethyl acetate (300 ml) was added to the mixture, which was washed with brine (3×150 ml). The organic layer was dried over MgSO4, and concentrated to yield N-methyl-2-fluoro-4-nitrobenzamide (52a) (2.89 g, 14.6 mmol, 91%) as a yellow solid. 1H NMR (Acetone d6, 400 MHz) δ 3.05 (d, J=4.3 Hz, 3H), 6.31 (dd, J=13.5, 2.1 Hz, 1H), 6.40 (dd, J=8.5, 2.1 Hz, 1H), 7.64 (dd, J=8.6, 8.6 Hz, 1H).

Workup

  1. distillationfreshly distilled from its 40% aqueous solution)
  2. additionwas added to the reaction medium
  3. stirringThe second mixture was stirred for an additional 1 hour
  4. additionEthyl acetate (300 ml) was added to the mixture, which
  5. washwas washed with brine (3×150 ml)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0ca35d23e3cd4183afb2ffae603eebaf
Source dataset
uspto-grants-2015_09
Patent number
US09126941B2

Reaction notes

Loading…