Tetrahydrofuran → 8-Methoxy-1,2,3,4-tetrahydroisoquinoline

HRID 131027Notes

Reaction equation

HRID 131027 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[C:11](=O)[NH:10][CH2:9][CH2:8]2.C1COCC1.[H-].[H-].[H-].[H-].[Li+].[Al+3].[OH-].[Na+]>O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:12]=1[CH2:11][NH:10][CH2:9][CH2:8]2

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 129507453,4-dihydro-8-Methoxyisoquinolin-1(2H)-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 129507478-Methoxy-1,2,3,4-tetrahydroisoquinolineYield 93%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Combine 8-Methoxy-3,4-dihydro-2H-isoquinolin-1-one (0.778 g, 4.40 mmol), THF (20 ml), and LiAlH4 (0.333 g, 8.8 mmol) at 0° C. under nitrogen atmosphere. After 30 minutes the reaction, reflux for 2 hours and then cool to room temperature. Quench the reaction by adding water and 1M NaOH at 0° C. and stirring for 12 hours at room temperature. Filter the reaction through celite and elute with THF. After concentrating the filtrate under reduced pressure, add the mixture to a 10 g SCX column pre-treated with 5% AcOH/MeOH. After rinsing several times with MeOH, elute the product using 1N NH3-MeOH followed by concentration under reduced pressure to afford 0.665 g, 4.07 mmol (93% yield) of the title compound as a tan oil: 1H NMR (500 MHz, CDCl3); 1.7-2.0 (1H, b s), 2.77 (2H, t, J=5.86), 3.09 (2H, t, J=5.86), 3.8 (3H, s), 3.95 (2H, s), 6.6-6.8 (2H, m), 7.0-7.15 (1H, m); TLC 5% MeOH:Ethyl acetate Rf:=0.1.

Workup

  1. customat 0° C.
  2. customAfter 30 minutes the reaction
  3. temperaturereflux for 2 hours
  4. customQuench
  5. customthe reaction
  6. filtrationFilter
  7. customthe reaction through celite and
  8. washelute with THF
  9. concentrationAfter concentrating the filtrate under reduced pressure
  10. additionadd the mixture to a 10 g SCX column
  11. additionpre-treated with 5% AcOH/MeOH
  12. washAfter rinsing several times with MeOH
  13. washelute the product
  14. concentrationfollowed by concentration under reduced pressure

Sources & evidence

ORD record
ord-9f8f6d4004db4254a88caabe98ffbd62
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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