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

HRID 1667185Notes

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[C:22]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:21][CH2:20][CH2:19][N:18]1[CH2:35][C:36](O)=O.Cl.C(N=C=NCCCN(C)C)C>ClCCCl>[C:29]1([C:22]2([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:21][CH2:20][CH2:19][N:18]([CH2:35][C:36]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:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide (0.033 g, 0.162 mmol), 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (Example 68E, 0.050 g, 0.162 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.046 g, 0.242 mmol) were stirred together in 1,2-dichloroethane (0.5 mL) at room temperature. After stirring for 1 hour, the reaction was heated to 85° C. and stirred overnight. The reaction was cooled, loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% ethyl acetate/hexane to 100% ethyl acetate over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 8.22-8.26 (m, 2H), 7.76-7.80 (m, 2H), 7.21-7.35 (m, 10H), 4.93 (s, 2H), 3.64 (t, J=6.4 Hz, 2H), 2.69-2.74 (m, 2H), 1.88-1.97 (m, 2H); MS (ESI+) m/z 478 (M+H)+.

Workup

stirringstirred overnight
temperatureThe reaction was cooled
washthe title compound was eluted
customover 20 minutes

Sources & evidence

ORD record: ord-4af93f14fce34aed9e2aab11c5d4e641
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

Loading…