1-(3-(Trifluoromethyl)phenyl)piperazine → 1-{4-[4-(3-Trifluoromethylphenyl)piperazin-1-yl]butyl}-1,5,6,7-tetrahydroindol-4-one

HRID 1835087Notes

Reaction equation

HRID 1835087 reaction equation
Cl[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:14]2[CH2:13][CH2:12][CH2:11][C:10](=[O:15])[C:9]=2[CH:8]=[CH:7]1.OC(C)(C)CC(=O)C.[I-].[Na+].[F:26][C:27]([F:41])([F:40])[C:28]1[CH:29]=[C:30]([N:34]2[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]2)[CH:31]=[CH:32][CH:33]=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C.ClCCl.C(OCC)(=O)C.ClCCl>[F:41][C:27]([F:26])([F:40])[C:28]1[CH:29]=[C:30]([N:34]2[CH2:39][CH2:38][N:37]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:14]4[CH2:13][CH2:12][CH2:11][C:10](=[O:15])[C:9]=4[CH:8]=[CH:7]3)[CH2:36][CH2:35]2)[CH:31]=[CH:32][CH:33]=1

Participants

9

Reactant 5

HCID 42961-(3-(Trifluoromethyl)phenyl)piperazineHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 31256Diacetone AlcoholHCID 235028891-(4-Chlorobutyl)-1,5,6,7-tetrahydroindol-4-one

Product 1

HCID 99318851-{4-[4-(3-Trifluoromethylphenyl)piperazin-1-yl]butyl}-1,5,6,7-tetrahydroindol-4-oneYield 91.5%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 21226138Dichloromethane ethylacetateSolvent

Procedure

A mixture of 1-(4-Chlorobutyl)-1,5,6,7-tetrahydroindol-4-one (6.0 g, 26.6 mmol, as a mixture with 3.0 g of 4-hydroxy-4-methyl-2-pentanone) and sodium iodide (4.38 g, 29.2 mmol) in acetonitrile (100 mL) was heated at reflux for 6 h. (3-Trifluoromethylphenyl)piperazine (5.81 g, 25.2 mmol) and potassium carbonate (3.67 g, 26.6 mmol) was then added and reflux continued for 16 h. TLC (ethyl acetate:dichloromethane 1:1) showed complete reaction. The reaction was poured into ice cold water (400 mL) and stirred for 0.5 h. An oil separated out and was isolated from the mixture. The oil was dissolved with dichloromethane (150 mL), washed with water and brine, then dried with sodium sulfate, filtered and the solvent removed under vacuum to yield the title compound as an oil (9.7 g, 91.5%).

Workup

  1. additionwas then added
  2. temperaturereflux
  3. customreaction
  4. customAn oil separated out
  5. customwas isolated from the mixture
  6. washwashed with water and brine
  7. dry with materialdried with sodium sulfate
  8. filtrationfiltered
  9. customthe solvent removed under vacuum

Sources & evidence

ORD record
ord-4b8bca94ec634a4d8da77fa4b45188a1
Source dataset
uspto-grants-2004_08
Patent number
US06770638B2

Reaction notes

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