Sodium Iodide → 5-(3,4-Difluorobenzyl)-2,3-dihydro-4-methoxycarbonyl-1-(5-(4-phenylpiperidin-1-yl)pent-1-yl)-2(1H)-imidazolone

HRID 1003746Notes

Reaction equation

HRID 1003746 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][N:7]1[C:11]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)=[C:10]([C:21]([O:23][CH3:24])=[O:22])[NH:9][C:8]1=[O:25].[C:26]1([CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>O1CCOCC1>[F:20][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][C:16]=1[F:19])[CH2:12][C:11]1[N:7]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:35]2[CH2:36][CH2:37][CH:32]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:33][CH2:34]2)[C:8](=[O:25])[NH:9][C:10]=1[C:21]([O:23][CH3:24])=[O:22]

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 698734-PhenylpiperidineHCID 187982741-(5-Bromopent-1-yl)-5-(3,4-difluorobenzyl)-2,3-dihydro-4-methoxycarbonyl-2(1H)-imidazolone

Product 1

HCID 187982675-(3,4-Difluorobenzyl)-2,3-dihydro-4-methoxycarbonyl-1-(5-(4-phenylpiperidin-1-yl)pent-1-yl)-2(1H)-imidazoloneYield 31.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 1-(5-bromopent-1-yl)-5-(3,4-difluorobenzyl)-2,3-dihydro-4-methoxycarbonyl-2(1H)-imidazolone (0.167 g, 0.4 mmol) in dioxane (20 mL) was added 4-phenylpiperidine (0.128 g, 0.800 mmol), potassium carbonate (0.165 g, 1.20 mmol) and sodium iodide (0.358 g, 2.38 mmol), and the solution refluxed for 24 hours. The reaction mixture was cooled to room temperature, concentrated and partitioned between ethyl acetate (25 mL) and water (5 mL) . The organic layer was dried over sodium sulfate, filtered and concentrated. The crude product was purified by column chromatography (ethyl acetate: methanol, 4.5:0.5) to yield 0.062 g (31%) of the required product as a colorless oil; 1H-NMR (CDCl3) δ1.25-2.44 (m, 13H), 3.13 (d, J=11.4 Hz, 2H), 3.26 (d, J=10.5 Hz, 2H), 3.53 (t, J=7.7 Hz, 2H), 3.85 (s, 3H), 4.10-4.12 (m, 1H), 4.21 (s, 2H), 6.90-7.30 (m, 8H). Hydrochloride salt (recrystallized from ether): yellow solid; m.p. 130-132° C. Analysis calculated for C28H34ClF2N3O3.0.80 CH2Cl2 : C, 57.46; H, 5.96; N, 6.98. Found: C, 57.18; H, 6.33; N, 6.76.

Workup

  1. temperaturethe solution refluxed for 24 hours
  2. concentrationconcentrated
  3. custompartitioned between ethyl acetate (25 mL) and water (5 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by column chromatography (ethyl acetate: methanol, 4.5:0.5)

Sources & evidence

ORD record
ord-4ec17a969063433db9af5965382b1677
Source dataset
uspto-grants-2000_04
Patent number
US06046331

Reaction notes

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