1. November 21 st 2006 by Isabelle Bonnaventure Literature MeetingCharette’s Laboratories Special Issue: Chem. Rev. 2006, vol. 7 An Overview of Process Chemistry or “Honey, I blew up the baby!”

2. Process Chemistry: Contents

3. Process Chemistry: General Considerations

5. Process Chemistry: Safety Issues

6. First Route: Second Route:

7. - 1994: explosion of a 70 gallon drum of H 2 O 2 Pfizer, Groton - 2002: explosion of BH 3 ·THF Process Chemistry: Safety Issues

8. Process Chemistry: General Considerations

10. Process Chemistry: Different Phases

12. Process Chemistry: High Throughput Equipment BASF: hydroformylation of olefin DSM: phosphoramidite ligands libraries Premex multireactor

13. Process Chemistry: High Throughput Equipment DSM: phosphoramidite screening in hydrogenation Dow: asymmetric hydroformylation

14. Process Chemistry: High Throughput Equipment Helgroup: HP auto  MATE

15. Process Chemistry: High Throughput Equipment BASF: Premex miniautoclave Simple laboratory plant for continuous processing

16. Process Chemistry: High Throughput Analysis

18. Process Chemistry: Ligand Synthesis

20. 250 L vessel for pilot  scale production of ligand 1 and 2 150 L vessel for pilot  scale production of ligand 3

21. Process Chemistry: Ligand Library

25. Process Chemistry: Legendary Example

32. Process Chemistry: Metal Removal

33. MS

34. Process Chemistry: Metal Removal

35. Process Chemistry: Survey General data: Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2004, 4, 2337-47.

36. Process Chemistry: Survey Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2004, 4, 2337-47. Summary of reaction categories: C-C bond forming reactions:

37. Process Chemistry: Survey Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2004, 4, 2337-47.

38. Process Chemistry: Survey Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org. Biomol. Chem. 2004, 4, 2337-47. Where does chirality come from?

39. Process Chemistry: Synthesis of CGS 19755

44. Process Chemistry: Synthesis of SB  214857  A

47. First scale  up route:

48. Process Chemistry: Synthesis of SB  214857  A Scale  up route:

49. Process Chemistry: Synthesis of SB  214857  A Never subjected to scale  up (clinical programme was halted at phase III) Alternative scale  up route:

50. Process Chemistry: Synthesis of SB-214857-A End of the synthesis:

51. Process Chemistry: Conclusion

53. Process Chemistry: Bulk Chemistry vs Fine Chemistry

54. Process Chemistry: High Throughput Experimentation