Synthesis of the NK1 receptor antagonist GW597599. Part 2: Development of a scalable route to a key chirally pure arylpiperazine

Organic Process Research and Development

Volumn 13, Issue 3, 2009, Pages 489-493

  Guercio, Giuseppe ^a   Manzo, Angelo Maria ^a   Goodyear, Michael ^a   Bacchi, Sergio ^a   Curti, Stefano ^a   Provera, Stefano ^a  

^a GSK   (Italy)

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EID: 66249115291     PISSN: 10836160     EISSN: 1520586X     Source Type: Journal    
DOI: 10.1021/op8002823     Document Type: Article

References (13)

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3. Burkhardt, E. R.; Corella, J. A., II. U.S. Patent 6,048,985, 2000.
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5. For a general review about methods of generating diborane in situ from sodium borohydride see: Souza, M. V. N.; Vasconcelos, T. R. A. Appl. Organomet. Chem. 2006, 20, 798.
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7. Endeavor, Argonaut, is a system made of eight reactor vessels with independent temperature and pressure controls. It works on a maximum scale of ∼5 mL, and it permits feeding a reactant in the closed vials, monitoring the pressure trend versus time.
8. Yadav, V. G.; Yadav, G. D.; Vyas, J. R. Chim. Oggi 2000, 18, 39.
9. The collected cake was washed with methanol to eliminate the alcohol derivative (see structure below) resulting from the reduction of residual mandelic acid.
10. Emsley, J.; Gold, V.; Lowe, B. M.; Szeto, W. T. A. J. Chem. Soc., Dalton Trans. 1988, 1271.
11. Hudlicky, M. J. Fluorine Chem. 1985, 28, 461.
12. Christe, K. O.; Wilson, W. W. J. Fluorine Chem. 1990, 46, 339.
13. Rushton turbines are radial impellers having a higher power number (NP) than other common impellers. The power number is a dimensionless number which describes the power supplied by an impeller. An empirical correlation relates NP to the effects of fluid viscosity. Considering the same fluid physical properties, stirrer speed, and impeller size, a Rushton turbine, having a higher NP, will supply more power to the fluid and, in general, is able to supply more intense mixing which should translate to a higher particles shear. Thus, on the basis of theoretical knowledge, the use of a Rushton turbine was recommended in the present case, requiring high intense mixing, in particular strong radial flow, and high particles shear.