Isopropanol → Voriconazole

Participants

Reaction Conditions

Reaction Steps

The wet product obtained in Example 1 (Voriconazole (1R)-(−)-10-camphorsulfonate, 41.49 g wet, 40.36 g dry estimated, 0.069 mol) was suspended in ethyl acetate (121 ml) and aqueous saturated sodium bicarbonate solution (97 ml) was added slowly. The mixture was stirred for 10 minutes, the phases allowed to settle and the organic layer separated. The aqueous layer was re-extracted with ethyl acetate (91 ml). The combined organic layers were washed with deionised water (12 ml), filtered and concentrated under vacuum until a white doughy residue was obtained. Isopropanol (24 ml) was added and concentrated again under vacuum until a white doughy residue was obtained. Isopropanol (54.5 ml) was added and the suspension was heated until complete solution (60-65° C.). The solution was cooled down to 0-2° C. and stirred for at least 1 hour. The suspension formed was filtered, the cake was washed with cold isopropanol (6.1 ml). A white crystalline solid was obtained after drying at 55-60° C. under vacuum until constant weight: 19.75 g (81.43% yield).

Provenance & Evidence