1-(Bis(4-fluorophenyl)methyl)piperazine → 1-(2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3-phenylpiperidin-2-one

HRID 1667178Notes

Reaction equation

HRID 1667178 reaction equation
[O:1]=[C:2]1[CH:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:6][CH2:5][CH2:4][N:3]1[CH2:14][C:15]([OH:17])=O.[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([C:32]2[CH:37]=[CH:36][C:35]([F:38])=[CH:34][CH:33]=2)[N:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:21][CH:20]=1.Cl.C(N=C=NCCCN(C)C)C>ClCCl>[F:38][C:35]1[CH:34]=[CH:33][C:32]([CH:25]([C:22]2[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=2)[N:26]2[CH2:27][CH2:28][N:29]([C:15](=[O:17])[CH2:14][N:3]3[CH2:4][CH2:5][CH2:6][CH:7]([C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:2]3=[O:1])[CH2:30][CH2:31]2)=[CH:37][CH:36]=1

Participants

5

Reactant 3

HCID 1529321-(Bis(4-fluorophenyl)methyl)piperazineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Product 1

HCID 452756021-(2-{4-[Bis(4-fluorophenyl)methyl]piperazin-1-yl}-2-oxoethyl)-3-phenylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 2-(2-oxo-3-phenylpiperidin-1-yl)acetic acid (Example 91D, 0.050 g, 0.214 mmol), 1-(bis(4-fluorophenyl)methyl)piperazine (0.068 g, 0.236 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.062 g, 0.322 mmol) in dichloromethane (0.5 mL) was allowed to stir at room temperature. After stirring overnight, the reaction was loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 15 minutes, maintaining 100% ethyl acetate for an additional 10 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 7.16-7.38 (m, 9H), 6.93-7.04 (m, 4H), 4.42 (d, J=15.5 Hz, 1H), 4.23 (s, 1H), 4.00 (d, J=15.5 Hz, 1H), 3.70 (dd, J=5.8, 4.6 Hz, 1H), 3.59-3.66 (m, 2H), 3.52-3.60 (m, 1H), 3.44-3.50 (m, 2H), 3.37-3.46 (m, 1H), 2.33-2.41 (m, 4H), 2.15-2.27 (m, 1H), 1.92-2.05 (m, 2H), 1.78-1.91 (m, 1H); MS (ESI−) m/z 502 (M−H)−.

Workup

  1. stirringAfter stirring overnight
  2. washthe title compound was eluted
  3. customover 15 minutes
  4. temperaturemaintaining 100% ethyl acetate for an additional 10 minutes (flow=30 mL/minute)

Sources & evidence

ORD record
ord-c9d088ab763d4a10943f5e4018fb4e09
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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