O-Xylene → 3-(4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhex-1-yl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline

HRID 979357

Reaction equation

HRID 979357 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([CH:34]([CH3:36])[CH3:35])([C:30](OC)=O)[CH2:12][CH2:13][CH2:14][CH:15]2[CH2:24][C:23]3[C:18](=[CH:19][C:20]([O:27][CH3:28])=[C:21]([O:25][CH3:26])[CH:22]=3)[CH2:17][N:16]2[CH3:29])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1(C)C(C)=CC=CC=1.[Al]([NH2:48])(C)C>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([CH:34]([CH3:35])[CH3:36])([C:30]#[N:48])[CH2:12][CH2:13][CH2:14][CH:15]2[CH2:24][C:23]3[C:18](=[CH:19][C:20]([O:27][CH3:28])=[C:21]([O:25][CH3:26])[CH:22]=3)[CH2:17][N:16]2[CH3:29])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

5

Reactant 3

HCID 7237O-Xylene3×HCID 16689643Aminodimethyl aluminium2×HCID 202022193-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-(carbomethoxy)butyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline3×

Product 1

HCID 1291023-(4-Cyano-4-(3,4-dimethoxyphenyl)-5-methylhex-1-yl)-1,2,3,4-tetrahydro-6,7-dimethoxy-2-methylisoquinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Alternatively, one may convert the ester group of compound 11.1 directly to the cyano group by treatment with 2 equivalents of dimethylaluminum amide (S. Weinreb, et al., Tetrahedron Lett., 4907 (1979), incorporated herein by reference). This reaction is performed in a suitable aprotic hydrocarbon solvent, preferably a high-boiling solvent such as xylene. Two equivalents of Me2AlNH2 in CH2Cl2 is added to a solution of the ester of formula 11.1 in the appropriate solvent and heated at 80°-170° C., preferably in refluxing xylene, for about 30 minutes to about 20 hours. The reaction is followed by TLC. For example, 3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-(carbomethoxy)butyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (11.1) is heated in refluxing xylene with Me2AlNH2 for about 15 hours to yield 3-[4-(3,4-dimethoxyphenyl)-4-isopropyl-4-cyanobutyl]-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (1).

Workup

  1. temperatureheated at 80°-170° C.
  2. waitfor about 30 minutes to about 20 hours

Sources & evidence

ORD record
ord-66caa6db2ccb47d080f1f86138199986
Source dataset
uspto-grants-1987_05
Patent number
US04667038

Linked notes

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