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

HRID 2407518Notes

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>[F:5][C:6]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:7]=1[C:8]([NH:19][CH3:18])=[O:9]

Participants

Conditions

Temperature: -5 °C

Procedure

Thionyl chloride (15 g, 130 mmol) was added slowly to a solution of acid 2-fluoro-4-nitro-benzoic acid (20 g, 110 mmol) in DMF (20 mL) at −5° C. The mixture was stirred for an additional 1 h at −5° C. At 0° C., a methylamine solution (2M, 400 mL, 800 mmol) in tetrahydrafuran was added drop-wise to the solution. The reaction mixture was slowly warmed to 25° C. and then poured into ice-water (125 mL). The suspension was extracted with ethyl acetate (2×200 mL). Combined organic phase was washed with brine (1×200 mL), dried (MgSO4) and concentrated to dryness in vacuo. The title compound 21 was obtained as a yellow solid (20 g, 90% yield). MS: 163 (M+H)+. 1H NMR (acetone-d6, 500 MHz): δ 7.66 (1H, dd, J=8.5, 8.5 Hz), 6.41 (1H, dd, J=8.6, 2.1 Hz), 6.32 (1H, dd, J=13.6, 2.0 Hz), 3.05 (3H, d, J=4.4 Hz).

Workup

temperatureThe reaction mixture was slowly warmed to 25° C.
extractionThe suspension was extracted with ethyl acetate (2×200 mL)
washCombined organic phase was washed with brine (1×200 mL)
dry with materialdried (MgSO4)
concentrationconcentrated to dryness in vacuo

Sources & evidence

ORD record: ord-997f1b38a10448e586bc27863900b576
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08809550B2

Reaction notes

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