Tetrahydrofuran → 6,7-Dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol

HRID 463724Notes

Reaction equation

HRID 463724 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=1)=[N:8][CH:7]=[C:6]2[C:26](O)=[O:27].O1CCCC1>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH2:15][C:16]1[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=1)=[N:8][CH:7]=[C:6]2[CH2:26][OH:27]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 135605336,7-Dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinolinecarboxylic acid

Product 1

HCID 135605346,7-Dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanolYield 84.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A slurry of 25.2 g of 6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinolinecarboxylic acid and 100 ml of dry tetrahydrofuran was stirred at 15° in an inert atmosphere while cautiously adding 200 ml of 1 molar borane/tetrahydrofuran complex. After stirring for 2 hours at room temperature, the initial solids had dissolved and were replaced by a second precipitate. The mixture was cautiously treated with 200 ml of water and the tetrahydrofuran was removed in vacuo at 40°. The chilled reaction mixture was then filtered, washed with water, and the damp stable borane complex was added portionwise with stirring to 200 ml of 2N hydrochloric acid previously heated to 70°-80°. The resulting solution was heated an additional 15 minutes on the steam bath and was then chilled and extracted with 100 ml of diethyl ether. The aqueous layer was added dropwise to 250 ml of cold 2N sodium hydroxide with stirring. The resulting solids were removed by filtration, washed well with water, and dried to give 20.6 g of crude 6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol, mp 146°-148°. Recrystallization from methylene chloride/ethyl acetate gave 19.2 g of purified 6,7-dimethoxy-1-[(3,4-dimethoxyphenyl)methyl]-4-isoquinoline methanol, mp 141°-143°.

Workup

  1. additionwhile cautiously adding 200 ml of 1 molar borane/tetrahydrofuran complex
  2. dissolutionthe initial solids had dissolved
  3. customthe tetrahydrofuran was removed in vacuo at 40°
  4. customThe chilled reaction mixture
  5. filtrationwas then filtered
  6. washwashed with water
  7. additionthe damp stable borane complex was added portionwise
  8. stirringwith stirring to 200 ml of 2N hydrochloric acid
  9. temperaturepreviously heated to 70°-80°
  10. temperatureThe resulting solution was heated an additional 15 minutes on the steam bath
  11. temperaturewas then chilled
  12. extractionextracted with 100 ml of diethyl ether
  13. additionThe aqueous layer was added dropwise to 250 ml of cold 2N sodium hydroxide
  14. stirringwith stirring
  15. customThe resulting solids were removed by filtration
  16. washwashed well with water
  17. customdried

Sources & evidence

ORD record
ord-9f452541a3b24c978a711e7b5bae9292
Source dataset
uspto-grants-1985_10
Patent number
US04544657

Reaction notes

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