Hydrochloric Acid → 3-carboethoxy-3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline

HRID 979367Notes

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].[Li+].CC([N-]C(C)C)C.[CH3:29][O:30][C:31]1[CH:32]=[C:33]([C:39]([CH:46]([CH3:48])[CH3:47])([CH2:42][CH2:43][CH2:44]I)[C:40]#[N:41])[CH:34]=[CH:35][C:36]=1[O:37][CH3:38].Cl>C1COCC1>[C:1]([C:6]1([CH2:44][CH2:43][CH2:42][C:39]([C:33]2[CH:34]=[CH:35][C:36]([O:37][CH3:38])=[C:31]([O:30][CH3:29])[CH:32]=2)([CH:46]([CH3:48])[CH3:47])[C:40]#[N:41])[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

Conditions

Temperature: 0 °C

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).

Workup

extractionthe product extracted
custompurified

Sources & evidence

ORD record: ord-1626a6cd0168476e84f3514f37a21788
Source dataset: uspto-grants-1987_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04667038

Reaction notes

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