N-(4-nitrophenethyl)-1,2,3,4-tetrahydro-7,8-dimethoxy-1-methylisoquinoline hydrochloride → Veradoline monohydrochloride
Reaction equation
[ClH:1].[N+:2]([C:5]1[CH:27]=[CH:26][C:8]([CH2:9][CH2:10][N:11]2[CH2:20][CH2:19][C:18]3[C:13](=[C:14]([O:23][CH3:24])[C:15]([O:21][CH3:22])=[CH:16][CH:17]=3)[CH:12]2[CH3:25])=[CH:7][CH:6]=1)([O-])=O>CO.O.[Pd].C(O)C>[ClH:1].[NH2:2][C:5]1[CH:27]=[CH:26][C:8]([CH2:9][CH2:10][N:11]2[CH2:20][CH2:19][C:18]3[C:17](=[CH:16][C:15]([O:21][CH3:22])=[C:14]([O:23][CH3:24])[CH:13]=3)[CH:12]2[CH3:25])=[CH:7][CH:6]=1Participants
Procedure
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°.
Workup
- additionadded under nitrogen
- customThe catalyst was removed by filtration
- customthe solvent evaporated
- customleaving an oily residue
- customhad crystallized out which
- filtrationwas collected by filtration and air
- customdried
Sources & evidence
- ORD record
- ord-e4821c01d1be418d9c84155703fed6c7
- Source dataset
- uspto-grants-1988_08
- Patent number
- US04766131
Reaction notes
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