[CH:1]1[C:6]([F:7])=[CH:5][C:4]2[CH2:8][CH2:9][CH:10]([CH:12]([OH:29])[CH2:13][NH:14][CH2:15][CH:16]([OH:28])[CH:17]3[O:26][C:25]4[CH:24]=[CH:23][C:22]([F:27])=[CH:21][C:20]=4[CH2:19][CH2:18]3)[O:11][C:3]=2[CH:2]=1.[ClH:30]>C(O)C>[CH:23]1[C:22]([F:27])=[CH:21][C:20]2[CH2:19][CH2:18][CH:17]([CH:16]([OH:28])[CH2:15][NH:14][CH2:13][CH:12]([OH:29])[CH:10]3[O:11][C:3]4[CH:2]=[CH:1][C:6]([F:7])=[CH:5][C:4]=4[CH2:8][CH2:9]3)[O:26][C:25]=2[CH:24]=1.[ClH:30]Nebivolol free base (3.30 g, 8.70 mmol) is suspended in absolute ethanol (100 mL) and heated to fall until complete dissolution. To this solution, 1.25 M ethanolic HCl (7.5 mL) is added. The obtained solution is concentrated under reduced pressure, until obtaining a 15% concentration of the product. During solvent evaporation, progressive formation of a white precipitate is observed. The solid is filtered by washing with cold absolute ethanol, to obtain 3.10 g of nebivolol hydrochloride salt. The chiral purity of the product and the ratio between the two enantiomers is evaluated by comparison with reference standards, by HPLC with an AKZO NOBEL column, Kromasil 5-AmyCoat, 5 μm, 250 mm×4.6 and a suitable binary gradient.
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