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46 results on '"Dolling U"'

24. Development of a Scaleable Synthesis of a 3-Aminopyrazinone Acetamide Thrombin Inhibitor

Author

Ashwood, M. S., Alabaster, R. J., Cottrell, I. F., Cowden, C. J., Davies, A. J., Dolling, U. H., Emerson, K. M., Gibb, A. D., Hands, D., Wallace, D. J., and Wilson, R. D.

Abstract

A scaleable route to 2-{3-[(2,2-difluoro-2-(2-pyridyl)ethyl)amino]-6-chloro-2-oxohydropyrazinyl}-N-[(3-fluoro(2-pyridyl))methyl]acetamide 1 is described in which various scaleup issues were addressed to provide a safe, efficient, and robust route for the preparation of multi-kilo amounts of the compound. The use of expensive and toxic reagents, notably sodium azide, TMS-cyanide, and Deoxo-Fluor, and the need for specialist equipment were overcome in the preparation of the key fluorinated intermediates 2,2-difluoro-2-(2-pyridyl)ethylamine 3 and 2-aminomethyl-3-fluoropyridine 2. With minimal isolations and through processing of intermediates, the thrombin inhibitor 1 was isolated in 36% overall yield.

Published
2004

25. A Double Ring Closing Metathesis Reaction in the Rapid, Enantioselective Synthesis of NK-1 Receptor Antagonists

Author

Wallace, D. J., Goodman, J. M., Kennedy, D. J., Davies, A. J., Cowden, C. J., Ashwood, M. S., Cottrell, I. F., Dolling, U.-H., and Reider, P. J.

Abstract

The NK-1 receptor antagonist 1 has been prepared in seven steps from phenylglycine methyl ester. The key steps are a double ring closing metathesis reaction of tetraene 7 to prepare spirocycle 6 and a reductive Heck reaction to introduce the aryl moiety. This latter reaction discriminates the olefins of compound 6 and proceeds in a highly regio- and stereoselective manner.

Published
2001

35. Practical Synthesis of Aryl Triflates under Aqueous Conditions

Author

Frantz, D. E., Weaver, D. G., Carey, J. P., Kress, M. H., and Dolling, U. H.

Abstract

A practical and efficient synthesis of aryl triflates under biphasic basic aqueous conditions is described. The current methodology provides entry into these valuable substrates that omits the use of amine bases and allows facile isolation by simple solvent evaporation after phase separation. Good yields can also be obtained without the use of organic solvent.

Published
2002

46. An improved preparation of 3,5-bis(trifluoromethyl)acetophenone and safety considerations in the preparation of 3,5-bis(trifluoromethyl)phenyl Grignard reagent.

Author

Leazer JL Jr, Cvetovich R, Tsay FR, Dolling U, Vickery T, and Bachert D

Abstract

An improved and efficient bromination of 3,5-bis(trifluoromethyl)benzene was developed. A safe and reliable preparation of the potentially explosive 3,5-bis(trifluoromethyl)phenyl Grignard and 3-trifluoromethylphenyl Grignard reagents, from the precursor bromides, is described. Reaction System Screening Tool (RSST) and Differential Thermal Analysis (DTA) studies suggest these trifluoromethylphenyl Grignard reagents can detonate on loss of solvent contact or upon moderate heating. When prepared and handled according to the methods described herein, these Grignard reagents can be safely prepared and carried on to advanced intermediates.

Published
2003
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