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

HRID 1667198Notes

Reaction equation

HRID 1667198 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][CH2:35][CH2:36][C:37](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][CH2:35][CH2:36][C:37]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

5

Reactant 3

HCID 609329N'-Hydroxy-4-(trifluoromethyl)benzene-1-carboximidamideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67360599HCID 67360599, compound

Product 1

HCID 673768173,3-Diphenyl-1-(3-{3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}propyl)pyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
85 °C

Procedure

A suspension of (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide (0.233 g, 1.143 mmol), 4-(2-oxo-3,3-diphenylpyrrolidin-1-yl)butanoic acid (0.336 g, 1.039 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.299 g, 1.559 mmol) were stirred together in dichloroethane (5 mL) for 3 hours then heated to 85° C. for 18 hours. The reaction was cooled and concentrated. The reaction was loaded onto a GraceResolv™ 40 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 4% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.17 (d, J=8.0, 2H), 7.73 (d, J=8.2, 2H), 7.38-7.20 (m, 10H), 3.56 (t, J=7.0, 2H), 3.41 (t, J=6.4, 2H), 2.92 (t, J=7.6, 2H), 2.77 (t, J=6.4, 2H), 2.22-2.09 (m, 2H); MS (ESI+) m/z 492.1 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. concentrationconcentrated
  3. washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 4% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record
ord-b0666f7d38f745d3985900c8c238ab74
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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