Progress in arylpiperazine synthesis by the catalytic amination reaction.
Careful base and solvent optimization for catalytic amination is described. A Pd-catalyzed amination between some arylbromide and unprotected piperazine (1equiv) was efficiently carried out with Pd/BINAP catalyst in a toluene-DBU solvent system, which is useful for the one-pot preparation of unsymmetrical piperazine through amination and in-situ N-protection. Reaction with N-BOC-piperazine was also successful in toluene-DBU or more polar NMP with Cs(2)CO(3) as a key base. No reports have previously reported such solvent and base optimization in arylpiperazine synthesis.
Torisawa
Yasuhiro
Y
Process Research Laboratory, Second Tokushima Factory, Otsuka Pharmaceutical Co. Ltd., Kawauchi-cho, Tokushima, Japan. torisawa@fact.otsuka.co.jp
Nishi
Takao
T
Minamikawa
Jun-ichi
J
D000586:Amination; D001555:Benzene Derivatives / Q000138:chemical synthesis; D002384:Catalysis; D007202:Indicators and Reagents; D009281:Naphthalenes / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D010879:Piperazines / Q000138:chemical synthesis*; D012997:Solvents / Q000737:chemistry
C406943:BINAP, 2-naphthol; D001555:Benzene Derivatives; D007202:Indicators and Reagents; D009281:Naphthalenes; D010879:Piperazines; D012997:Solvents; D010165:Palladium