3-Chloro-4-fluoroaniline → N-(3-chloro-4-fluorophenyl)-4-(hydroxymethyl)-1,2,5-oxadiazole-3-carboxamide

HRID 2097605Notes

Reaction equation

[N:1]1[O:2][N:3]=[C:4]2[C:8](=[O:9])[O:7][CH2:6][C:5]=12.CN(C)C(=O)C.[Cl:16][C:17]1[CH:18]=[C:19]([CH:21]=[CH:22][C:23]=1[F:24])[NH2:20]>CCO>[Cl:16][C:17]1[CH:18]=[C:19]([NH:20][C:8]([C:4]2[C:5]([CH2:6][OH:7])=[N:1][O:2][N:3]=2)=[O:9])[CH:21]=[CH:22][C:23]=1[F:24]

Participants

Conditions

Temperature: 80 °C

Procedure

4H,6H-Furo[3,4-c][1,2,5]oxadiazol-4-one (2.00 g, 0.0159 mol) was dissolved in EtOH (80 mL) and N,N-dimethylacetamide (10 mL) and then 3-chloro-4-fluoroaniline (2.5 g, 0.017 mol) was added as a solid. The reaction was heated at 80° C. overnight. The crude reaction mixture was concentrated in vacuo. The oil was extracted twice with EtOAc and washed with water. The organic was dried over Na2SO4 and concentrated. The crude residue was purified by flash column chromatography eluting with EtOAc:Hexane (1:1) to yield the desired product (3.2 g, 74%). 1H NMR (400 MHz, DMSO-d6) δ: 11.30 (s, 1H), 8.30 (dd, J=7.0, 2.7 Hz, 1H), 7.69 (ddd, J=9.1, 4.4, 2.6 Hz, 1H) 7.45 (dd, J=9.1, 9.1 Hz, 1H), 4.86 (d=5.8 Hz, 2H), 5.78 (t, 5.8 Hz, 1H); MF═C10H7ClFN3O3; LCMS calculated for C10H8ClFN3O3(M+H)+: m/z=272.024.

Workup

customThe crude reaction mixture
concentrationwas concentrated in vacuo
extractionThe oil was extracted twice with EtOAc
washwashed with water
dry with materialThe organic was dried over Na2SO4
concentrationconcentrated
customThe crude residue was purified by flash column chromatography
washeluting with EtOAc:Hexane (1:1)

Sources & evidence

ORD record: ord-872cee65adf94de3ad391fc2b0f95d40
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08450351B2

Reaction notes

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