Trifluoroacetic acid → 1-(2-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline

HRID 2383026Notes

Reaction equation

HRID 2383026 reaction equation
N[C@@H]1C2C(=CC=CC=2)C[C@@H]1O.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[C:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][N:21]=1.FC(F)(F)C(O)=O>C(OCC)C>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[CH:20]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][NH:21]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 2725045(1R,2S)-(+)-cis-1-Amino-2-indanolHCID 675387781-(2-Methoxyphenyl)-3,4-dihydroisoquinoline

Product 1

HCID 242573611-(2-Methoxyphenyl)-1,2,3,4-tetrahydroisoquinolineYield 81.6%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
5 °C

Procedure

Under an argon atmosphere, a 1.0 M borane-THF complex solution (110 mL) was added to a mixture of (1R,2S)-1-amino-2-indanol (8.17 g) and diethyl ether (200 mL) under stirring at an internal temperature of 5° C. or lower. The mixture was further stirred at room temperature for 1.5 hours. The mixture was cooled to an internal temperature of 4° C. 1-(2-methoxyphenyl)-3,4-dihydroisoquinoline (10 g) was gradually added to the mixture at an internal temperature of 5° C. or lower, followed by stirring at the same temperature for 30 minutes. The mixture was stirred at room temperature for 3 days. Trifluoroacetic acid (61 mL) was added to the reaction mixture to decompose an excess of reagent, further followed by heating under reflux for 3 hours. After cooling, diethyl ether was evaporated under reduced pressure and the mixture was heated under reflux for 10 minutes. The residue was diluted with chloroform and extracted with concentrated aqueous ammonia to be alkaline. The organic layer was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform-EtOH-aqueous ammonia) to obtain 1-(2-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline (8.23 g).

Workup

  1. stirringThe mixture was further stirred at room temperature for 1.5 hours
  2. temperatureThe mixture was cooled to an internal temperature of 4° C
  3. stirringby stirring at the same temperature for 30 minutes
  4. stirringThe mixture was stirred at room temperature for 3 days
  5. temperatureby heating
  6. temperatureunder reflux for 3 hours
  7. temperatureAfter cooling
  8. customdiethyl ether was evaporated under reduced pressure
  9. temperaturethe mixture was heated
  10. temperatureunder reflux for 10 minutes
  11. additionThe residue was diluted with chloroform
  12. extractionextracted with concentrated aqueous ammonia
  13. washThe organic layer was washed with saturated brine
  14. dry with materialdried over magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customThe resulting residue was purified by silica gel column chromatography (chloroform-EtOH-aqueous ammonia)

Sources & evidence

ORD record
ord-e2cd944fee1c4154a2526cf5391a3344
Source dataset
uspto-grants-2012_09
Patent number
US08263607B2

Reaction notes

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