Chapter 3. Liberties and Constraints in the Development of Asymmetric Hydrogenations on a Technical Scale

Summary

This chapter contains sections titled:

• Introduction

• Asymmetric Hydrogenation in the Lonza Biotin Process

  • Historical Development

  • Laboratory Screening Experiments

    • Ligand Screening

    • Substrate Screening

    • Parameter Screening and Optimization

  • Scale-up and Production

  • Preparation of Josiphos (R)-(S)-PPF-P(^tBu)₂ on a Technical Scale

  • Conclusions

• The Lonza Dextrometorphan Process

  • Introduction

  • Imine Hydrogenation

    • Background

    • Screening Experiments

    • Optimization Phase: Development of an Economic Process

  • Scale-up

  • Conclusion

• 4-Boc-piperazine-2(S)-N-^tbutylcarboxamide

  • Introduction

  • Initial Studies

  • Scale-up

  • Further Improvements in Synthetic Strategy

  • Conclusions

• Intermediates for SB-214857 (Lotrafiban)

  • Introduction

  • Initial Screening of Catalysts

  • Statistically Evaluated Screening of Experimental Conditions