Piperazine → Vortioxetine

HRID 508277Notes

Reaction equation

HRID 508277 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[SH:9].[NH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.Br[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1I.BrC1C=CC=CC=1Br.CC([O-])(C)C.[Na+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[S:9][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1

Participants

9

Reactant 6

HCID 4837PiperazineHCID 114141,2-DibromobenzeneHCID 114151-Bromo-2-iodobenzeneHCID 836172,4-DimethylbenzenethiolHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxide

Product 1

HCID 9966051Vortioxetine

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent2×

Procedure

In one embodiment, 1-1.5 equivalents of 2,4-dimethylthiophenol, piperazine, and one of 1-bromo-2-iodo benzene and 1,2-dibromo-benzene are dispersed in toluene followed by the addition of 2-5, such as 3 equivalents NaOt-Bu and 1-2 Mole-% Pd2dba3 and rac-BINAP dispersed in toluene to obtain a mixture which is refluxed for 2-10 hours, typically 3-5 hours to obtain 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine. Optionally, this product may be further reacted with aqueous HBr to achieve the corresponding hydrobromic acid addition salt.

Workup

  1. customto obtain a mixture which
  2. temperatureis refluxed for 2-10 hours, typically 3-5 hours

Sources & evidence

ORD record
ord-9c064b552c664fc4a468497e7c116b12
Source dataset
uspto-grants-2015_08
Patent number
US09095588B2

Reaction notes

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