Benzhydrylpiperazine → 1-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethyl]-3-phenylpiperidin-2-one

HRID 1667177Notes

Reaction equation

HRID 1667177 reaction equation
[CH:1]([N:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O:20]=[C:21]1[CH:26]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH2:25][CH2:24][CH2:23][N:22]1[CH2:33][C:34](O)=[O:35].C(N(C(C)C)CC)(C)C>ClCCl>[CH:1]([N:14]1[CH2:19][CH2:18][N:17]([C:34](=[O:35])[CH2:33][N:22]2[CH2:23][CH2:24][CH2:25][CH:26]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]2=[O:20])[CH2:16][CH2:15]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 70048BenzhydrylpiperazineHCID 81531DiisopropylethylamineHCID 673587022-(2-Oxo-3-phenylpiperidin-1-yl)acetic acid

Product 1

HCID 452753901-[2-(4-Benzhydrylpiperazin-1-yl)-2-oxoethyl]-3-phenylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 1-benzhydrylpiperazine (0.238 g, 0.943 mmol), the product from Example 91D (0.200 g, 0.857 mmol) and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (0.358 g, 0.943 mmol) in dichloromethane (1.5 mL) was added diisopropylethylamine (0.225 mL, 1.286 mmol), and the reaction mixture was stirred at room temperature. After stirring overnight, the reaction was concentrated and loaded onto a silica gel column (SF25-25, Analogix®, Burlington, Wis.) and eluted using a gradient of 0.5% to 5% methanol/dichloromethane. The product was isolated along with a slightly lower Rf spot. The mixture was rechromatographed over silica gel using a gradient of 5% to 100% ethyl acetate/hexanes to supply the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 7.38-7.43 (m, 4H), 7.14-7.34 (m, 11H), 4.43 (d, J=15.6 Hz, 1H), 4.24 (s, 1H), 4.00 (d, J=15.6 Hz, 1H), 3.70 (dd, J=7.7, 6.0 Hz, 1H), 3.61-3.66 (m, 2H), 3.52-3.59 (m, 1H), 3.44-3.49 (m, 2H), 3.41 (dd, J=11.6, 5.8 Hz, 1H), 2.37-2.43 (m, 4H), 2.15-2.28 (m, 1H), 1.90-2.03 (m, 2H), 1.77-1.89 (m, 1H); MS (ESI+) m/z 468 (M+H)+.

Workup

  1. stirringAfter stirring overnight
  2. concentrationthe reaction was concentrated
  3. washeluted
  4. customThe product was isolated along with a slightly lower Rf spot
  5. customThe mixture was rechromatographed over silica gel using a gradient of 5% to 100% ethyl acetate/hexanes to supply the title compound

Sources & evidence

ORD record
ord-80531d70565e4eaaa4af4333400ec532
Source dataset
uspto-grants-2011_10
Patent number
US08044069B2

Reaction notes

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