Nitrilase-catalysed desymmetrisation of 3-hydroxyglutaronitrile: Preparation of a statin side-chain intermediate

Organic Process Research and Development

Volumn 10, Issue 3, 2006, Pages 661-665

  Bergeron, Sophie ^a   Chaplin, David A ^a   Edwards, John H ^a   Ellis, Brian S W ^a   Hill, Catherine L ^a   Holt Tiffin, Karen ^a   Knight, Jonathan R ^a   Mahoney, Thomas ^a   Osborne, Andrew P ^a   Ruecroft, Graham ^a,b  

^a DOW CHEMICAL COMPANY   (United States)

^b C3 Technology   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 33745747626     PISSN: 10836160     EISSN: None     Source Type: Journal    
DOI: 10.1021/op050257n     Document Type: Article

References (16)

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5. (b) Davis, S. C.; Jenne, S. J.; Krebber, A.; Huisman, G. W.; Newman, L. M. WO 05017135, 2005.
6. (c) Davis, S. C.; Fox, R. J.; Gavrilovic, V.; Huisman, G. W.; Newman, L. M. WO 05017141, 2005.
7. (d) Davis, S. C.; Grate, J. H.; Gray, D. R.; Gruber, J. M.; Huisman, G. W.; Ma, S. K.; Newman, L. M.; Sheldon, R.; Wang, L. A. WO 05018579, 2005.
8. (a) DeSantis, G.; Zhu, Z.; Greenberg, W.; Wong, K.; Chaplin, J.; Hanson, S.; Farwell, B.; Nicholson, L.; Rand, C.; Weiner, D.; Robertson, D.; Burk, M. J. Am. Chem. Soc. 2002, 124, 9024.
9. (b) DeSantis, G.; Wong, K.; Farwell, B.; Chatman, K.; Zhu, Z.; Tomlinson, G.; Huang, H.; Tan, X.; Bibbs, L.; Chen, P.; Kretz, K.; Burk, M. J. Am. Chem. Soc. 2003, 125, 11476.
10. Epichlorohydrin is unstable in the presence of acid or base. In this reaction, base catalyst and water are charged to the reaction vessel. Hydrolysis of the epichlorohydrin is possible, but in the worst case, autopolymerisation may occur. For these reasons the inventory of epichlorohydrin present is minimized by batch feeding. HCN is batch fed in all processes. When acid stabilised, HCN may be considered inert. However, in the presence of catalytic quantities of any base, cyanide ion is generated which initiates polymerisation of HCN. In the worst case, explosive polymerisation may occur. For this reason the inventory of HCN is minimized by batch feeding. The enthalpy of reaction (for the required reaction) was estimated at ∼100 kJ/mol. Trie reaction diluent, water, provides a good heat sink, but the reaction power is controlled by feed rate and efficient cooling.
11. Singh, J.; Simms, C. Institution of Chemical Engineers Symposium Series 148, Hazards XVI; Institution of Chemical Engineers, 2001; pp 67-79.
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13. 2; oven program: 75 °C (hold 5 min), heat to 275 °C @ 10 °C/min, hold for 5 min; CHBN elutes at 10.7 min.
14. 2; oven program: 75 °C (hold 5 min), heat to 275 °C @ 10 °C/min, hold for 5 min; CHBN elutes at 10.7 min, HGN elutes at 14.5 min.
15. GC assay: DB-1701 column; injector temperature, 250 °C; detector temperature, 300 °C; carrier gas, He @ 15 psi; oven program: 60 °C (hold 5 min), heat to 220 °C @ 5 °C/min; 1 elutes at 19.6 min.
16. GC assay: Chiraldex G-TA column; injector temperature, 180 °C; detector temperature, 180 °C; carrier gas, He @ 14 psi; oven program: 150 °C (hold for 10 min), heat to 180 °C @ 10 °C/min, hold for 10 min; (R)-enantiomer elutes at 9.66 min; (S)-enantiomer elutes at 9.44 min.