2.   Lithiated or grignard difluorobenzene to Fluconazole

Although this reaction produces flucanzole in greater yield it has many setbacks making it an unattractive method of synthesis.  To prepare the 1-lithiated derivative of 1-bromo-2,4-diflurorobenzene requires the use of highly moisture and air sensitive, flammable and corrosive n-butyl lithium.  Other hazards in preparation of gignards or lithium reagents is the solvents required, diethyl ether or THF (tetrahydrofuran) which are extremely flammable.  The dihaloacetone is highly toxic and corrosive also.  This makes this procedure highly unattractive for large-scale commercial production as the reagents and solvents would be extremely hazardous in large volumes.

1. Conversion an epoxide to Fluconazole  2.   Lithiated or grignard difluorobenzene to Fluconazole
3.   Laboratory suitable method    4.   Commercially viable method: Sulphate process