Process development of voriconazole: a novel broad-spectrum triazole antifungal agent

M Butters, J Ebbs, SP Green, J MacRae…

Index: Butters, Mike; Ebbs, Julie; Green, Stuart P.; MacRae, Julie; Morland, Matthew C.; Murtiashaw, Charles W.; Pettman, Alan J. Organic Process Research and Development, 2001 , vol. 5, # 1 p. 28 - 36

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Citation Number: 58

Abstract

In the synthesis of (2 R, 3 S)-2-(2, 4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1 H-1, 2, 4- triazol-1-yl)-2-butanol (voriconazole), the relative stereochemistry is set in the addition of a 4- (1-metalloethyl)-5-fluoropyrimidine derivative to 1-(2, 4-difluorophenyl)-2-(1 H-1, 2, 4-triazol- 1-yl)-1-ethanone. The diastereocontrol of this reaction has been examined by variation of pyrimidine substitution pattern and by changes in the metalation and reaction conditions. ...