Sodium Hydroxide → (R)-(5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-yl)methanol

HRID 1854548Notes

Reaction equation

HRID 1854548 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][C@H:12]([C:19](O)=[O:20])[NH:13][CH2:14]2.[OH-].[Na+].S([O-])([O-])(=O)=O.[Mg+2]>O1CCCC1.O>[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:15]2[C:10]=1[CH2:11][C@H:12]([CH2:19][OH:20])[NH:13][CH2:14]2

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 24083Sulfuric acid magnesium salt (1:1)HCID 21226445Aluminium lithium hydrideHCID 117720332(R)-5-Bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride

Product 1

HCID 117720341(R)-(5-Bromo-1,2,3,4-tetrahydroisoquinolin-3-yl)methanolYield 49.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

Add lithium aluminum hydride (2 L, 2.00 mol, 1M in THF) to (3R)-5-bromo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid hydrochloride (325.4 g, 1.11 mol) in tetrahydrofuran (4.88 L) at −35° C. in an appropriate vessel, then warm to 25° C. over 60 minutes and stir. After 3 hours, cool the mixture to −5° C. then add water (76 mL), 15% w/w aqueous sodium hydroxide (76 mL) and water (228 mL). Heat the mixture to 25° C., add anhydrous magnesium sulfate (750 g) and stir. Filter the mixture and concentrate under reduced pressure to give a solid. Add dichloromethane (690 mL) to the solid and slurry for 30 minutes before filtration to give a solid. Dry the solid under vacuum at 35° C. to give the title compound (148.9 g, 0.55 mol). MS (m/z): 242(M+1 (79Br)), 244(M+1 (81Br)).

Workup

  1. temperaturecool the mixture to −5° C.
  2. temperatureHeat the mixture to 25° C.
  3. stirringstir
  4. filtrationFilter the mixture
  5. concentrationconcentrate under reduced pressure
  6. customto give a solid
  7. filtrationAdd dichloromethane (690 mL) to the solid and slurry for 30 minutes before filtration
  8. customto give a solid
  9. customDry the solid under vacuum at 35° C.

Sources & evidence

ORD record
ord-18d3bb271f564c2185ef4e1f33ca7451
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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