Acetic Acid → Isavuconazole

Participants

Reaction Conditions

Reaction Steps

A solution of the racemic 3-[4-(4-cyanophenyl)thiazol-2-yl]-1-(1H-1,2,4-triazol-1-yl)-2-(2,5-difluorophenyl)-butan-2-ol (4.4 g) and (1R)-10-camphorsulfonic acid (2 g) in toluene (40 ml) containing glacial acetic acid (0.6 ml) was warmed up to approximately 70° C., then allowed to cool slowly to 20° C., seeded with the pure enantiomeric salt whereupon the pure enantiomeric salt start to crystallize out. After ca. 2 hrs at this temperature the solid was collected, washed with cold toluene and dried. The crystals were taken with a solvent mixture of methylenechloride/water and after addition of aqueous saturated sodium bicarbonate solution the organic phase was separated and aqueous phase washed twice with methylenechloride. The combined organic phases were filtrated and the solvent removed under reduced pressure. Recrystallization of the crude product from aqueous ethanol provided enantiomerically pure title compound: 2 g (45% yield, 99% ee). The analytical data were identical with published: U.S. Pat. No. 6,300,353 and WO 99/45008.

Provenance & Evidence