反应详情

温度

-10 °C

169.9 g (0.420 mol theoretical) crude terbinafine (example 22) is dissolved in 306 ml methyl ethyl ketone (MEK) at 20/25° C.; then 41.3 ml (1 eq.) of 32% aqueous HCl are added dropwise at 20/30° C. Crystallisation of the product takes place during addition. The suspension is stirred for 15 minutes and then concentrated to a small volume under vacuum at 40° C. to azeotropically eliminate the water present, it is subsequently made up twice with MEK and again concentrated to a small volume under vacuum at 40° C. and finally diluted with MEK to restore it to the initial volume. The suspension is then cooled to −10° C. and stirred for 3 hours. The precipitate is filtered, washed with 2×69 ml cold MEK and dried to constant weight under vacuum at 40° C. 103.3 g (0.317 mol, 75% yield) terbinafine hydrochloride are obtained as a white crystalline solid with purity of 99.8% (HPLC A %) and a melting point of 207° C.-208° C.

1. customCrystallisation of the product
2. additionduring addition
3. concentrationconcentrated to a small volume under vacuum at 40° C.
4. concentrationagain concentrated to a small volume under vacuum at 40° C.
5. additionfinally diluted with MEK
6. stirringstirred for 3 hours
7. filtrationThe precipitate is filtered
8. washwashed with 2×69 ml cold MEK
9. customdried to constant weight under vacuum at 40° C