N'-Hydroxy-4-(trifluoromethyl)benzene-1-carboximidamide → 3-Phenyl-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-2-one

HRID 1667221Notes

Reaction equation

[OH:1][NH:2]/[C:3](=[N:14]\[H])/[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1.[O:16]=[C:17]1[CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][N:18]1[CH2:29][C:30](O)=O.Cl.C(N=C=NCCCN(C)C)C>ClC(Cl)C>[C:23]1([CH:22]2[CH2:21][CH2:20][CH2:19][N:18]([CH2:29][C:30]3[O:1][N:2]=[C:3]([C:4]4[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=4)[N:14]=3)[C:17]2=[O:16])[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide (0.142 g, 0.698 mmol), 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (0.148 g, 0.634 mmol; Example 91D) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.158 g, 0.825 mmol) were stirred together in dichloroethane (0.5 mL) at room temperature for 2 hours. The reaction was then heated to 85° C. and stirred overnight. The reaction was cooled, loaded onto a SF15-12 column (Analogix®) and the product eluted using a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate over 25 minutes (Flow=30 mL/minute). The residue was dissolved in ethyl acetate and concentrated to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.23 (d, J=8.2, 2H), 7.77 (d, J=8.3, 2H), 7.42-7.15 (m, 5H), 5.19 (d, J=16.7, 1H), 4.73 (d, J=16.7, 1H), 3.84-3.76 (m, 1H), 3.70 (ddd, J=5.3, 7.6, 12.7, 1H), 3.59 (dt, J=5.5, 11.2, 1H), 2.43-2.18 (m, 1H), 2.18-1.82 (m, 3H); MS (ESI+) m/z 402.0 (M+H)+.

Workup

temperatureThe reaction was cooled
washthe product eluted
customover 25 minutes
dissolutionThe residue was dissolved in ethyl acetate
concentrationconcentrated

Sources & evidence

ORD record: ord-eaab8facb34b477280a00f1ab1da9c67
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

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