3,5-Dimethylbenzoic acid → methyl N-(3,5-dimethylbenzoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate

HRID 1957016Notes

Reaction equation

HRID 1957016 reaction equation
Cl.[CH2:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH:4]([C:12]([O:14][CH3:15])=[O:13])[NH:3]1.[CH3:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:20](O)=[O:21].CN(C)CCCN=C=NCC>CN(C=O)C.C(OCC)(=O)C>[CH3:16][C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([CH3:26])[CH:25]=1)[C:20]([N:3]1[CH:4]([C:12]([O:14][CH3:15])=[O:13])[CH2:5][C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:2]1)=[O:21]

Participants

6

Reactant 3

HCID 103563,5-Dimethylbenzoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 122480673-Isoquinolinecarboxylic acid, 1,2,3,4-tetrahydro-, methyl ester, hydrochloride (1:1)

Product 1

HCID 18663440methyl N-(3,5-dimethylbenzoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of methyl 1,2,3,4-tetrahydro-3-isoquinolinecarboxylate hydrochloride (2.0 g, 9 mmol) and 3,5-dimethylbenzoic acid (1.6 g, 10 mmol) in DMF (15 ml) is treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (1.9 ml, 10 mmol). The reaction mixture is slowly warmed to r.t. and stirring continued for 2 hours. The homogeneous mixture is diluted with ethyl acetate (500 ml) and washed with three portions of water (200 ml). The organic layer is dried over magnesium sulfate, filtered and concentrated in vacuo. The crude material is chromatographed on silica with ethyl acetate/hexane 1:3 to give methyl N-(3,5-dimethylbenzoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylate as a colorless oil. This material is hydrolized with 1M sodium hydroxide in THF to give N-(3,5-dimethylbenzoyl)-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid as a white solid.

Workup

  1. washwashed with three portions of water (200 ml)
  2. dry with materialThe organic layer is dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material is chromatographed on silica with ethyl acetate/hexane 1:3

Sources & evidence

ORD record
ord-24145c0dbfd34e3ab4140f3900a41dca
Source dataset
uspto-grants-1998_07
Patent number
US05780498

Reaction notes

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