Ammonium Chloride → 1-(3,5-Bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-imidazole-4-carboxylic acid methoxy-N-methyl-amide

HRID 349271Notes

Reaction equation

CO[C:3]([C:5]1[N:6]=[CH:7][N:8]([CH2:16][C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([C:27]([F:30])([F:29])[F:28])[CH:18]=2)[C:9]=1[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:4].Cl.[CH3:32][NH:33][O:34][CH3:35].C([Mg]Cl)(C)C.[NH4+].[Cl-]>C1COCC1>[CH3:35][O:34][N:33]([CH3:32])[C:3]([C:5]1[N:6]=[CH:7][N:8]([CH2:16][C:17]2[CH:18]=[C:19]([C:27]([F:28])([F:30])[F:29])[CH:20]=[C:21]([C:23]([F:25])([F:24])[F:26])[CH:22]=2)[C:9]=1[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1)=[O:4]

Participants

Conditions

Temperature: 0 °C

Procedure

Combine 1-(3,5-Bis-trifluoromethyl-benzyl)-5-pyridin-3-yl-1H-imidazole-4-carboxylic acid methyl ester (0.46 g, 1.1 mmol) and N,O-dimethyl-hydroxylamine-HCl (0.16 g, 1.6 mmol) in THF (5.5 mL). Chill to 0° C., then slowly add isopropyl magnesium chloride (2M/THF, 1.6 mL, 3.2 mmol). After 45 min., warm to RT. Add 70% sat. aq. NH4Cl, and extract with EtOAc. Dry over MgSO4, filter, and concentrate. Purify by flash chromatography on silica gel to give the title compound: MS (ES) 459.2 (M+1); 1H NMR (300 MHz, CDCl3) δ 8.63 (d, J=4.8 Hz, 1H), 8.52 (app d, 1H), 7.79 (s, 1H), 7.73 (s, 1H), 7.63 (app d, J=8.1 Hz, 1H), 7.35–7.31 (m, 1H), 7.30 (s, 2H), 5.21 (s, 2H), 3.79 (s, 3H), 3.37 (br s, 3H).

Workup

temperaturewarm to RT
extractionextract with EtOAc
dry with materialDry over MgSO4
filtrationfilter
concentrationconcentrate
customPurify by flash chromatography on silica gel

Sources & evidence

ORD record: ord-1d620498278a43cfb22537f8241c13f0
Source dataset: uspto-grants-2007_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07179804B2

Reaction notes

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