Sodium hydride → 2-Benzyl-3-methyl-8-phenyl-1,2,3,4-tetrahydroisoquinoline

HRID 27243Notes

Reaction equation

S([O-])(=O)(=O)C.[CH2:6]([N:13]1[CH:22]([CH3:23])[CH2:21][C:20]2[C:15](=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:17]=[CH:18][CH:19]=2)[C:14]1=O)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[H-].[Na+].[H-].[Al+3].[Li+].[H-].[H-].[H-]>>[CH2:6]([N:13]1[CH:22]([CH3:23])[CH2:21][C:20]2[C:15](=[C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH:17]=[CH:18][CH:19]=2)[CH2:14]1)[C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1

Participants

Reactant 4

HCID 24758Sodium hydride

HCID 85257Methanesulfonate

HCID 21226445Aluminium lithium hydride

HCID 233443682-benzyl-3,4-dihydro-3-methyl-8-phenyl-1(2H)-isoquinolone

Product 1

HCID 504692-Benzyl-3-methyl-8-phenyl-1,2,3,4-tetrahydroisoquinoline

Procedure

Heating 3,4-dihydro-3-methyl-8-phenylisocoumarin and benzylamine hydrobromide in benzylamine at 160° C. gives N-benzyl-6-(2-hydroxy-2-methylethyl)2-biphenylcarboxamide which is converted to the corresponding mesylate and then cyclized to 2-benzyl-3,4-dihydro-3-methyl-8-phenyl-1(2H)-isoquinolone with sodium hydride. This compound is then reduced with lithium aluminum hydride to give 2-benzyl-3-methyl-8-phenyl-1,2,3,4-tetrahydroisoquinoline. Hydrogenation of this product using 5% palladium-on-carbon on the catalyst affords 3-methyl-8-phenyl-1,2,3,4-tetrahydroisoquinoline. Reacting 3-methyl-8-1,2,3,4-tetrahydroisoquinoline with formaldehyde and formic acid affords 2,3-dimethyl-8-phenyl-1,2,3,4-tetrahydroisoquinoline.

Sources & evidence

ORD record: ord-6ff6e2682ead46f4aa005c54b40163f2
Source dataset: uspto-grants-1980_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04220778

Reaction notes

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