Potassium Iodide → 5-Fluoro-3-(1-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}piperidin-4-ylmethyl)-1H-indole

HRID 1108208

Reaction equation

HRID 1108208 reaction equation
C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[CH2:19][CH:20]1[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]1.Cl[CH2:27][CH2:28][N:29]1[CH2:34][CH2:33][N:32]([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=2[O:41][CH3:42])[CH2:31][CH2:30]1>C(#N)C.O>[F:9][C:10]1[CH:11]=[C:12]2[C:16](=[CH:17][CH:18]=1)[NH:15][CH:14]=[C:13]2[CH2:19][CH:20]1[CH2:25][CH2:24][N:23]([CH2:27][CH2:28][N:29]2[CH2:30][CH2:31][N:32]([C:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=3[O:41][CH3:42])[CH2:33][CH2:34]2)[CH2:22][CH2:21]1

Participants

7

Reactant 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 5956731-(2-Chloroethyl)-4-(2-methoxyphenyl)piperazineHCID 112877165-fluoro-3-[(4-piperidinyl)methyl]-1H-indole

Product 1

HCID 98250155-Fluoro-3-(1-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}piperidin-4-ylmethyl)-1H-indoleYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Procedure

Pulverized potassium carbonate (0.76 g, 5.5 mmole) and potassium iodide (0.97 g, 5.5 mmole) was added to a mixture of 4-(5-fluoro-1H-indol-3-ylmethyl)piperidine (1.16 g, 5.0 mmole) and 1-(2-chloroethyl)-4-(2-methoxyphenyl)piperazine (1.27 g, 5.0 mmole) in 25 ml of acetonitrile. The resulting mixture was heated to reflux under nitrogen for 5 hours. After cooling, it was diluted with water (150 ml) and the product extracted into ethyl acetate (50 ml). The organic layer was washed with water (50 ml), brine (50 ml), and after drying over sodium sulfate, filtration and concentration in vacuo afforded the required product as a white solid (1.8 g, 80%). Treatment with an excess of 1M etheral hydrochloric acid gave the acid addition salt, which was recrystallized from methanol.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux under nitrogen for 5 hours
  3. temperatureAfter cooling
  4. extractionthe product extracted into ethyl acetate (50 ml)
  5. washThe organic layer was washed with water (50 ml), brine (50 ml)
  6. dry with materialafter drying over sodium sulfate, filtration and concentration in vacuo

Sources & evidence

ORD record
ord-c57ffb01e9a7445d9a831e48cdd8bab1
Source dataset
uspto-grants-2000_05
Patent number
US06066637

Linked notes

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