Phenol → 1-Phenoxy-6-bromomethyl-isoquinoline

HRID 651642Notes

Reaction equation

HRID 651642 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH3:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.CC1C=C2C(C=CNC2=O)=CC=1.[C:25]1([OH:31])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.[OH-].[K+].C1C(=O)N([Br:41])C(=O)C1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>C(Cl)Cl>[O:31]([C:2]1[C:11]2[C:6](=[CH:7][C:8]([CH2:12][Br:41])=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1

Participants

8

Reactant 6

HCID 996PhenolHCID 7187Benzoyl PeroxideHCID 14797Potassium HydroxideHCID 67184N-bromobutanimideHCID 156938767-Methylisoquinolin-1(2H)-oneHCID 219277691-Chloro-6-methylisoquinoline

Product 1

HCID 181763341-Phenoxy-6-bromomethyl-isoquinoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To 1-chloro-6-methyl-isoquinoline (2.28 g, 13.3 mmol), which is prepared as described in EXAMPLE 1, Part E, substituting 6-methyl-2H-isoquinolin-1-one for 7-methyl-2H-isoquinolin-1-one, is added 20 g of phenol. The solution is heated to 80° C. and KOH (3.73 g, 66.4 mmol) is added. After the addition, the solution is stirred and heated to 140° C. After 24 hours, the solution is cooled to ambient temperatures, and dissolved in CH2Cl2. The organic solution is washed with H2O. The organic layer is washed with 1 N NaOH and saturated NaCl. the organic layer is dried over MgSO4, filtered and concentrated. The resulting residue is dissolved in 50 mL of CCL4. To the resulting solution is added NBS (2.01 g, 11.27 mmol) and benzoyl peroxide (0.6 g, 1.73 mmol). The solution is heated to reflux. After 16 hours, the solution is diluted with CH2Cl2. The organic layer is washed with 10% Na2CO3 and saturated NaCl. The organic layer is dried over MgSO4, filtered and concentrated. The residue is purified by column chromatography eluting with 5% EtOAc/hexanes and 10% EtOAc/hexanes.

Workup

  1. additionAfter the addition
  2. temperatureheated to 140° C
  3. temperaturethe solution is cooled to ambient temperatures
  4. washThe organic solution is washed with H2O
  5. washThe organic layer is washed with 1 N NaOH and saturated NaCl
  6. dry with materialthe organic layer is dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe resulting residue is dissolved in 50 mL of CCL4
  10. temperatureThe solution is heated to reflux
  11. waitAfter 16 hours
  12. washThe organic layer is washed with 10% Na2CO3 and saturated NaCl
  13. dry with materialThe organic layer is dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe residue is purified by column chromatography
  17. washeluting with 5% EtOAc/hexanes and 10% EtOAc/hexanes

Sources & evidence

ORD record
ord-83269b9c1a6a4731b2f0d27da9fb2aaf
Source dataset
uspto-grants-2001_08
Patent number
US06281227B1

Reaction notes

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