Dimethylformamide → 4-(2-fluoro-4-nitrophenyl)-N,N-dimethylbutanamide

HRID 1192871Notes

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)[CH3:23]>>[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]([N:22]([CH3:23])[CH3:21])=[O:20]

Participants

Reactant 3

HCID 6228Dimethylformamide

HCID 24386Thionyl Chloride

HCID 576726244-(2-Fluoro-4-nitrophenyl)butanoic acid

Product 1

HCID 687351604-(2-fluoro-4-nitrophenyl)-N,N-dimethylbutanamideYield 87%

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) (18 mg, 0.08 mmol) in DMF (3 mL) cooled at −5° C. The mixture was stirred for an additional 1 h at −5° C. Excess dimethylamine (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,N-dimethylbutanamide (77) (18 mg, 87%): 1H NMR δ 7.98 (dd, 1H, J=8.3, 2.1 Hz), 7.89 (dd, 1H, J=9.5, 2.1 Hz), 7.42 (dd, 1H, J=8.3, 7.4 Hz), 2.98 (s, 3H), 2.95 (s, 3H), 2.81 (t, 2H, J=7.6 Hz) 2.36 (t, 2H, J=7.2 Hz) 1.96-2.04 (m, 2H).

Workup

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

Sources & evidence

ORD record: ord-34c694e14a64453b8896cad14433113c
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680291B2

Reaction notes

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