Hydrochloric Acid → HCID 67045907, compound

HRID 606320Notes

Reaction equation

HRID 606320 reaction equation
C[O:2][C:3]1[C:4]([CH3:25])=[C:5]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]([CH:20](O)[CH2:21][CH2:22][CH3:23])=[CH:12][N:11]=2)[C:6]([CH3:9])=[CH:7][CH:8]=1.[H-].[Na+].C(I)C.B(Br)(Br)[Br:32].Cl.[OH-].[Na+]>CN(C=O)C.C(Cl)Cl.CO.O>[Br:32][CH:20]([C:13]1[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:10]([C:5]2[C:4]([CH3:25])=[C:3]([OH:2])[CH:8]=[CH:7][C:6]=2[CH3:9])=[N:11][CH:12]=1)[CH2:21][CH2:22][CH3:23]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 6340IodoethaneHCID 14798Sodium HydroxideHCID 24758Sodium hydrideHCID 25134Boron tribromideHCID 67046249HCID 67046249, compound

Product 1

HCID 67045907HCID 67045907, compoundYield 94.6%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

A solution of 1-[1-(3-methoxy-2,6-dimethyl-phenyl)-isoquinolin-4-yl]-butan-1-ol (117 mg, 0.33 mmol) in DMF (2 ml) is added to a suspension of NaH (67 mg, 60% dispersion in mineral oil, 1.7 mmol) in DMF (4 ml) at 0° C. After stirring for 45 min, EtI (0.26 ml, 3.3 mmol) is added slowly. After stirring for 10 min at 0° C., the mixture is allowed to warm to room temperature and the stirring is continued for 1 h. Water is added and the mixture is extracted with Et2O. The combined extracts are washed with saturated brine, dried over Na2SO4, and concentrated to give the desired ether that is dissolved in DCM (12 ml). After cooling to −78° C., BBr3 (3.2 ml of 1 M solution in DCM, 3.2 mmol) is added dropwise and the mixture is allowed to warm to room temperature. After stirring for 1 h, MeOH (3 ml) and 1N—HCl (50 uL) are added carefully. After heating for 10 min at 80° C., the mixture is cooled and then basified with 1N—NaOH to pH 10. The resulting mixture is extracted with DCM and the combined extracts are washed with saturated brine. Drying over Na2SO4 and concentration are followed by flash chromatography to give 120 mg of 3-[4-(1-bromo-butyl)-isoquinolin-1-yl]-2,4-dimethyl-phenol as a yellow foam.

Workup

  1. stirringAfter stirring for 10 min at 0° C.
  2. waitthe stirring is continued for 1 h
  3. extractionthe mixture is extracted with Et2O
  4. washThe combined extracts are washed with saturated brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto give the desired ether that
  8. temperatureAfter cooling to −78° C.
  9. temperatureto warm to room temperature
  10. stirringAfter stirring for 1 h
  11. temperatureAfter heating for 10 min at 80° C.
  12. temperaturethe mixture is cooled
  13. extractionThe resulting mixture is extracted with DCM
  14. washthe combined extracts are washed with saturated brine
  15. dry with materialDrying over Na2SO4 and concentration

Sources & evidence

ORD record
ord-8de3827e7b104f90b98288166723619d
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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