2-(3,4-Dimethoxyphenyl)-2-isopropyl-2-(3-iodopropyl)acetonitrile → 3-carboethoxy-3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline
Reaction equation
[C:1]([CH:6]1[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:18][CH3:19])=[C:12]([O:16][CH3:17])[CH:13]=2)[CH2:8][N:7]1[CH3:20])([O:3][CH2:4][CH3:5])=[O:2].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([C:31]([CH:38]([CH3:40])[CH3:39])([CH2:34][CH2:35][CH2:36]I)[C:32]#[N:33])[CH:26]=[CH:27][C:28]=1[O:29][CH3:30]>>[C:1]([C:6]1([CH2:36][CH2:35][CH2:34][C:31]([C:25]2[CH:26]=[CH:27][C:28]([O:29][CH3:30])=[C:23]([O:22][CH3:21])[CH:24]=2)([CH:38]([CH3:40])[CH3:39])[C:32]#[N:33])[CH2:15][C:14]2[C:9](=[CH:10][C:11]([O:18][CH3:19])=[C:12]([O:16][CH3:17])[CH:13]=2)[CH2:8][N:7]1[CH3:20])([O:3][CH2:4][CH3:5])=[O:2]Participants
Reactant 2
Product 1
Procedure
The resulting ester of formula 31 is then treated with an iodoalkane of formula 22 (see Scheme III, step 2) in the presence of a strong base to form an alkylated tetrahydroisoquinoline ester of formula 32. For example, 3-carboethoxy-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (31) is added to a solution of LDA in THF at -70° C. and allowed to stand for 5-60 minutes, preferably about 10 minutes. To this reaction mixture is then added 2-(3,4-dimethoxyphenyl)-2-isopropyl-2-(3-iodopropyl)acetonitrile (22) in THF, and the resulting mixture allowed to warm to about 0° C. The mixture is then acidified, for example with dilute HCl, and the product extracted and purified to produce 3-carboethoxy-3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (32).
Sources & evidence
- ORD record
- ord-c1379ce37e0f4f09afac9ee9dd0cb7fc
- Source dataset
- uspto-grants-1987_05
- Patent number
- US04667038
Reaction notes
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