4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-mercapto-1h-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile and processes of preparation
Provided herein is a process for the preparation of 4-((6-(2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-mercapto-1H-1,2,4-triazol-1-yl)propyl)pyridin-3-yl)oxy)benzonitrile.
1. A method of making a compound of Formula I
comprising the step of contacting a compound of Formula II
with a base, elemental sulfur, and an acid;
wherein the contacting is carried out between 100° C. and −40° C.
2. The method of claim 1 , wherein the base is selected from the group consisting of: LiHMDS, NaHMDS, KHMDS, LDA, LTMP, and mixtures thereof.
3. The method of claim 1 , wherein the base is selected from the group consisting of: lithium t-butoxide, sodium t-butoxide, potassium t-butoxide, and mixtures thereof.
4. The method of claim 1 , wherein the base is selected from the group consisting of: lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, and mixtures thereof.
5. The method of claim 2 , further comprising a solvent selected from the group consisting of: THF, DME, ether, MTBE, 2-Me-THF, hexanes, dioxane, toluene, and mixtures thereof.
6. The method of claim 1 wherein the acid is selected from the group consisting of: HCl, HBr, H 2 SO 4 , H 3 PO 4 , HNO 3 , acetic acid, trifluoroacetic acid, and mixtures thereof.