Bromide ion → 3-[4-[1-(4-Fluorophenyl)-4-piperazinyl]butyl]-4-thiazolidinone

HRID 2107460Notes

Reaction equation

HRID 2107460 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10](=[O:11])[CH2:9][S:8][CH2:7]1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+].[Br-]>[Na+].[I-].CO.C(Cl)(Cl)Cl.CC#N>[F:12][C:13]1[CH:14]=[CH:15][C:16]([N:19]2[CH2:24][CH2:23][N:22]([CH2:2][CH2:3][CH2:4][CH2:5][N:6]3[C:10](=[O:11])[CH2:9][S:8][CH2:7]3)[CH2:21][CH2:20]2)=[CH:17][CH:18]=1

Participants

8

Reactant 4

HCID 259Bromide ionHCID 11430Potassium CarbonateHCID 752601-(4-Fluorophenyl)piperazineHCID 108475053-(4-Bromobutyl)-4-thiazolidinone

Product 1

HCID 107593943-[4-[1-(4-Fluorophenyl)-4-piperazinyl]butyl]-4-thiazolidinoneYield 69.2%

Reagents, catalysts & solvents 3

HCID 5238Sodium IodideCatalystHCID 6342AcetonitrileSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3-(4-bromobutyl)-4-thiazolidinone (4.01 g), 1-(4-fluorophenyl)piperazine (3.35 g), K2CO3 (4.64 g), NaI (150 mg) and CH3CN (150 ml) was heated at 100° C. (bath temperature) under N2 for 18 h. TLC analysis (silica gel, 8% MeOH/CHCl3) showed one major product at Rf =0.36, and the absence of starting bromide. The reaction mixture was cooled to room temperature and concentrated in vacuo to an oil which was taken up in EtOAc. The mixture was filtered to remove the precipitate and the filtrate concentrated in vacuo to an amber oil which solidified under vacuum. The solid (5.86 g) was dissolved in CHCl3 and flash chromatographed (silica gel) and thereafter recrystallized from hexane/CH2Cl2 to yield in two crops 3.93 g of white crystals, mp 83°-85° C. TLC analysis showed a trace of slower moving impurity. Recrystallization from hexane/CH2Cl2 afforded 3.1 g of white needles which were still slightly impure by TLC. The material was again flash chromatographed (silica gel) and recrystallized from hexane/CH2Cl2 to give 2.67 g of pure product, mp 84°-85° C.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated in vacuo to an oil which
  3. filtrationThe mixture was filtered
  4. customto remove the precipitate
  5. concentrationthe filtrate concentrated in vacuo to an amber oil which
  6. dissolutionThe solid (5.86 g) was dissolved in CHCl3
  7. customflash chromatographed (silica gel)
  8. customrecrystallized from hexane/CH2Cl2

Sources & evidence

ORD record
ord-b9f320bcf1b84746a195766fbb4d061b
Source dataset
uspto-grants-1990_06
Patent number
US04933453

Reaction notes

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