4-(Trifluoromethyl)benzoic acid → HCID 67376786, compound

HRID 1667235Notes

Reaction equation

HRID 1667235 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.O[NH:15]/[C:16](=[N:36]\[H])/[CH2:17][N:18]1[CH2:22][CH2:21][C:20]([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)[C:19]1=[O:35].Cl.C(N=C=NCCCN(C)C)C>ClC(Cl)C.C(OCC)(=O)C>[C:29]1([C:20]2([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:21][CH2:22][N:18]([CH2:17][C:16]3[N:15]=[C:7]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:13])[F:12])=[CH:11][CH:10]=4)[O:9][N:36]=3)[C:19]2=[O:35])[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 99664-(Trifluoromethyl)benzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 178506475HCID 178506475, compound

Product 1

HCID 67376786HCID 67376786, compound

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

4-(Trifluoromethyl)benzoic acid (0.416 g, 2.187 mmol), (Z)—N-hydroxy-2-(2-oxo-3,3-diphenylpyrrolidin-1-yl)acetimidamide (0.451 g, 1.458 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.559 g, 2.92 mmol) in dichloroethane were stirred together at room temperature for 3 hours. The reaction was then heated to 85° C. and stirred at this temperature for 16 hours. The reaction was cooled, poured in ethyl acetate/1 N HCl (1:1, 200 mL) and the layers separated. The organic layer was washed with brine (100 mL), dried over magnesium sulfate and concentrated. The residue was loaded onto a GraceResolv™ 12 g silica gel column (Grace Davison Discovery Sciences) and eluted with a gradient of 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.20 (d, J=8.3, 2H), 7.80 (d, J=8.4, 2H), 7.48-7.15 (m, 10H), 4.81 (s, 2H), 3.50 (t, J=6.5, 2H), 2.84 (t, J=6.5, 2H); MS (ESI+) m/z 464.1 (M+H)+.

Workup

  1. temperatureThe reaction was cooled
  2. customthe layers separated
  3. washThe organic layer was washed with brine (100 mL)
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. washeluted with a gradient of 5% ethyl acetate/hexanes to 35% ethyl acetate/hexanes (flow=40 mL/minute) over 30 minutes

Sources & evidence

ORD record
ord-b019ec904a2a4fc7a9e16ad69aebc816
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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