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

HRID 1667128Notes

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

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide (0.579 g, 2.84 mmol), 2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetic acid (Example 1C, 0.762 g, 2.58 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.594 g, 3.10 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 SF25-40 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 30% ethyl acetate/hexanes over 30 minutes (flow=40 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 8.09-8.15 (m, 2H), 7.71-7.76 (m, 2H), 7.23-7.43 (m, 10H), 4.91 (s, 2H), 3.58 (t, J=6.5 Hz, 2H), 2.90 (t, J=6.4 Hz, 2H); MS (ESI−) m/z 462 (M−H)−.

Workup

temperatureThe reaction was cooled
washthe title compound was eluted
customover 30 minutes

Sources & evidence

ORD record: ord-2f57ec7a34954d1faea46b7149e839d1
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

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