Dimethylformamide → 4-(2-fluoro-4-nitrophenyl)-N-methylbutanamide

HRID 1192867Notes

Reaction equation

HRID 1192867 reaction equation
S(Cl)(Cl)=O.[F:5][C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:7]=1[CH2:15][CH2:16][CH2:17][C:18]([OH:20])=O.[CH3:21][N:22](C=O)C>>[F:5][C:6]1[CH:11]=[C:10]([N+:12]([O-:14])=[O:13])[CH:9]=[CH:8][C:7]=1[CH2:15][CH2:16][CH2:17][C:18]([NH:22][CH3:21])=[O:20]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 576726244-(2-Fluoro-4-nitrophenyl)butanoic acid

Product 1

HCID 687330104-(2-fluoro-4-nitrophenyl)-N-methylbutanamideYield 85%

Conditions

Temperature
-5 °C

Procedure

Thionyl chloride (0.01 mL, 0.11 mmol) was added slowly to a solution of 4-(2-Fluoro-4-nitrophenyl)butanoic acid (82) (20 mg, 0.09 mmol) in DMF (3 mL) cooled at −5° C. The mixture was stirred for an additional 1 h at −5° C. Excess methylamine (freshly distilled from its 40% aqueous solution) was added to the reaction medium. The second mixture was stirred for an additional 1 h. Ethyl acetate (30 mL) was added to the mixture, which was washed with brine (2×30 mL). The organic layer was dried over MgSO4, and concentrated to yield 4-(2-Fluoro-4-nitrophenyl)-N-methylbutanamide (81) (18 mg, 85%): 1H NMR δ 7.97 (dd, 1H, J=8.4, 2.2 Hz), 7.89 (dd, 1H, J=9.5, 2.2 Hz), 7.40 (dd, 1H, J=8.4, 7.3 Hz), 5.44 (br s, 1H), 2.81 (d, 3H, J=4.9 Hz) 2.79 (t, 2H, J=7.6 Hz) 2.22 (t, 2H, J=7.3 Hz) 1.96-2.04 (m, 2H).

Workup

  1. distillationExcess methylamine (freshly distilled from its 40% aqueous solution)
  2. additionwas added to the reaction medium
  3. stirringThe second mixture was stirred for an additional 1 h
  4. additionEthyl acetate (30 mL) was added to the mixture, which
  5. washwas washed with brine (2×30 mL)
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-577ca1aa18e24ac08b91e2bfa6be45ed
Source dataset
uspto-grants-2014_03
Patent number
US08680291B2

Reaction notes

Loading…