N-(4-nitrophenethyl)-1,2,3,4-tetrahydro-7,8-dimethoxy-1-methylisoquinoline hydrochloride → Veradoline monohydrochloride

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Reaction Steps

A solution of N-(4-nitrophenethyl)-1,2,3,4-tetrahydro-7,8-dimethoxy-1-methylisoquinoline hydrochloride (66.3 g, 0.17 m) in methanol (1 liter) and water (10 ml) was placed in an 1100 ml pressure bottle and 5% Pd/C catalyst (5.0 g) added under nitrogen. The mixture was hydrogenated at 40 psi in a Parr apparatus for 20 hr. The catalyst was removed by filtration and the solvent evaporated leaving an oily residue. The residue was dissolved in 95% ethanol (300 ml) and after 24 hr a solid had crystallized out which was collected by filtration and air dried giving 44.3 g (82%) of N-(4-aminophenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline monohydrochloride. The free base could be obtained by basifying a solution of this salt with NaOH and extracting with CHCl3. Evaporation of the solvent and crystallization of the resulting oil from cyclohexane gives the base in 80% efficiency as a white solid. Melting point after drying at 60° for 26 hr under high vacuum 102°-103°.

Provenance & Evidence