Hydrochloric Acid → 8-(3-Chloromethylbenzyloxy)-2-formyl-6,7-dimethoxy-1-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2379449Notes

Reaction equation

HRID 2379449 reaction equation
[H-].[Na+].[CH:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[C:8]([OH:19])[C:9]([O:17][CH3:18])=[C:10]([O:15][CH3:16])[CH:11]=2)[CH:6]1[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=1)=[O:4].Cl.[Cl:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([CH2:38]Cl)[CH:33]=1>CS(C)=O.O>[Cl:30][CH2:31][C:32]1[CH:33]=[C:34]([CH:35]=[CH:36][CH:37]=1)[CH2:38][O:19][C:8]1[C:9]([O:17][CH3:18])=[C:10]([O:15][CH3:16])[CH:11]=[C:12]2[C:7]=1[CH:6]([CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([O:27][CH3:28])[CH:22]=1)[N:5]([CH:3]=[O:4])[CH2:14][CH2:13]2

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 12275Benzene, 1,3-bis(chloromethyl)-HCID 24758Sodium hydrideHCID 189570292-Formyl-6,7-dimethoxy-1-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-8-ol

Product 1

HCID 189570358-(3-Chloromethylbenzyloxy)-2-formyl-6,7-dimethoxy-1-(3-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 962WaterSolvent

Procedure

To a suspension of sodium hydride (80 mg, 1.96 mmole, 60%) in dimethyl sulfoxide (1 ml) was added a solution of intermediate 2 obtained in Referential Example 2 (350 mg, 0.98 mmole) at room temperature under nitrogen, and the reaction mixture was stirred for 10 minutes. The resulting mixture was added dropwise to a solution of α,α'-dichloro-m-xylene (172 mg, 0.98 mmole) in dimethyl sulfoxide (1 ml) at room temperature, and stirred for 2 hours. The reaction mixture was chilled in ice, diluted with water, and extracted with ethyl acetate. The combined organic layers were dried over MgSO4, and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel/ethyl acetate) to give the desired compound (387 mg) as a pale yellow oil.

Workup

  1. stirringstirred for 2 hours
  2. temperatureThe reaction mixture was chilled in ice
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by column chromatography (silica gel/ethyl acetate)

Sources & evidence

ORD record
ord-392a236aac95476bbc045a143dae417b
Source dataset
uspto-grants-1994_11
Patent number
US05362736

Reaction notes

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