Hydrogen Bromide → HCID 57761092, compound

HRID 230960Notes

Reaction equation

HRID 230960 reaction equation
[CH3:1][N:2]1[CH2:11][C:10]([CH3:13])([CH3:12])[C:9]2[C:4](=[CH:5][C:6](N)=[CH:7][CH:8]=2)[CH2:3]1.N([O-])=O.[Na+].[BrH:19]>OS(O)(=O)=O.O>[Br:19][C:6]1[CH:5]=[C:4]2[C:9]([C:10]([CH3:13])([CH3:12])[CH2:11][N:2]([CH3:1])[CH2:3]2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 260Hydrogen BromideHCID 18382547HCID 18382547, compoundHCID 23668193Sodium Nitrite

Product 1

HCID 57761092HCID 57761092, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1118Sulfuric AcidSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled solution of 2,4,4-trimethyl-1,2,3,4-tetrahydro-isoquinolin-7-ylamine (prepared essentially as described in PCT International Application Publication Numbers WO 00/009,486, WO 00/007,993 or WO 98/41507; 330 mg, 1.734 mmol) in 75% aqueous H2SO4, add NaNO2 (132 mg, 1.91 mmol) in 1 ml of water, dropwise. Stir the solution at 0° C. for 30 minutes. Add CuBr (298 mg, 2.08 mmol) and 48% HBr (2 ml). Stir the mixture at 0° C. for 15 minutes. Heat the mixture at 60° C. for 30 minutes. Cool to room temperature, adjust the pH to 9-10, and extract with EtOAc. Wash with brine, dry the solution (Na2SO4), and concentrate under reduced pressure. Purify the residue by flash column chromatography eluting with EtOAc:Hexanes-(1:1) to afford 7-bromo-2,4,4-trimethyl-1,2,3,4-tetrahydro-isoquinoline.

Workup

  1. stirringStir the mixture at 0° C. for 15 minutes
  2. temperatureHeat the mixture at 60° C. for 30 minutes
  3. temperatureCool to room temperature
  4. extractionextract with EtOAc
  5. washWash with brine
  6. dry with materialdry the solution (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. customPurify the residue by flash column chromatography
  9. washeluting with EtOAc:Hexanes-(1:1)

Sources & evidence

ORD record
ord-72ad198a92244789989e4b287d277b1b
Source dataset
uspto-grants-2009_07
Patent number
US07566712B2

Reaction notes

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