Asymmetric Hydrogenation vs. Resolution in the Synthesis of POSICOR®, a New Type of Calcium Antagonist


  • Yvo Crameri
  • Joseph Foricher
  • Urs Hengartner
  • Christian-Johannes Jenny
  • Frank Kienzle
  • Henri Ramuz
  • Michelangelo Scalone
  • Markus Schlageter
  • Rudolf Schmid
  • Shaoning Wang



The pilot-plant-scale synthesis of (S)-2-(4-fluorophenyl)-3-methylbutanoic acid by asymmetric hydrogenation of 2-(4-fluorophenyl)-3-methylbut-2-enoic acid with the [Ru((R)-MeOBIPHEP)(OAc)2]-catalyst is described. The hydrogenation was performed in a continuous mode in a cascade stirred-tank reactor system at 270 bar pressure. The (S)-2-(4-fluorophenyl)-3-methylbutanoic acid is an important optically active intermediate in the synthesis of mibefradil, a new type of calcium antagonist.




How to Cite

Y. Crameri, J. Foricher, U. Hengartner, C.-J. Jenny, F. Kienzle, H. Ramuz, M. Scalone, M. Schlageter, R. Schmid, S. Wang, Chimia 1997, 51, 303, DOI: 10.2533/chimia.1997.303.