Hydrochloric Acid → Terbinafine Hydrochloride

HRID 1175206Notes

Reaction equation

[CH3:1][C:2]([C:5]#[C:6]/[CH:7]=[CH:8]/[CH2:9][N:10]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=12)[CH3:11])([CH3:4])[CH3:3].[ClH:23]>C(C(C)=O)C>[CH3:4][C:2]([C:5]#[C:6]/[CH:7]=[CH:8]/[CH2:9][N:10]([CH2:12][C:13]1[CH:14]=[CH:15][CH:16]=[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=12)[CH3:11])([CH3:1])[CH3:3].[ClH:23]

Participants

Conditions

Temperature: -10 °C

Procedure

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.

Workup

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

Sources & evidence

ORD record: ord-ca70d0925c354b5e871fa203bad7a681
Source dataset: uspto-grants-2010_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07838704B2

Reaction notes

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