Sodium Iodide → 4-(4-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidine

HRID 411508Notes

Reaction equation

HRID 411508 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[F:17][C:18]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:19]=1[CH2:20][CH2:21]Br.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CC#N>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([CH:11]2[CH2:16][CH2:15][N:14]([CH2:21][CH2:20][C:19]3[CH:23]=[CH:24][C:25]([F:27])=[CH:26][C:18]=3[F:17])[CH2:13][CH2:12]2)(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 27610704-(4-Bromobenzenesulfonyl)piperidineHCID 112989892,4-Difluorophenethyl bromide

Product 1

HCID 110485124-(4-Bromophenylsulphonyl)-1-[2-(2,4-difluorophenyl)ethyl]piperidineYield 58.5%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture of 4-(4-bromophenylsulphonyl)piperidine (7.6 g, 0.025 mol), 2,4-difluorophenethyl bromide (8.3 g, 0.38 mol), potassium carbonate (7.5 g, 0.054 mol) and sodium iodide (5.6 g, 0.037 mol) in CH3CN (70 ml) was heated at reflux under nitrogen for 18 h. The reaction mixture was then concentrated and partitioned between water and EtOAc. The organic phase was washed with brine, dried (Na2SO4) and concentrated. Trituration with hexane gave 6.5 g of product as a colourless solid. δH (360 MHz, CDCl3) 1.55-1.75 (2H, m), 1.95-2.05 (4H, m), 2.45-2.55 (2H, m), 2.70-2.75 (2H, m), 2.85-2.95 (1H, m), 3.05-3.10 (2H, m), 6.70-6.85 (2H, m), 7.10-7.15 (1H, m), 7.72 (4H, s).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 18 h
  3. concentrationThe reaction mixture was then concentrated
  4. custompartitioned between water and EtOAc
  5. washThe organic phase was washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6e17553d45f04d11b4745cae1c98e5f1
Source dataset
uspto-grants-2003_05
Patent number
US06559166B1

Reaction notes

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