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

HRID 130934Notes

Reaction equation

HRID 130934 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 of the reaction, reflux for 2 hours and then cool to room temperature. Quench the reaction by adding water and 1.0 M 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 1.0 N 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 Hz), 3.09 (2H, t, J=5.86 Hz), 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 of the reaction
  3. temperaturereflux for 2 hours
  4. customQuench
  5. customthe reaction
  6. filtrationFilter
  7. customthe reaction through Celite®
  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-5cba0982172e494898441968bc6213a1
Source dataset
uspto-grants-2008_06
Patent number
US07381719B2

Reaction notes

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