Potassium Hydroxide → HCID 178486669, compound

HRID 1620145Notes

Reaction equation

HRID 1620145 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH3:15])=[N:8][C:7]([OH:16])=[CH:6]2.[OH-].[K+].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[CH:23][CH:22]=1>C1(C)C=CC=CC=1.O.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[C:9]([CH3:15])=[N:8][C:7]([OH:16])=[C:6]2[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)=[CH:23][CH:22]=1

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 15142511-(Bromomethyl)-4-phenoxybenzeneHCID 178486704HCID 178486704, compound2×

Product 1

HCID 178486669HCID 178486669, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6,7-dimethoxy-1-methylisoquinolin-3-ol CCH 18060 (152 mg, 693 μmol) in toluene (15 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.38 mL, 0.76 mmol) at RT followed by 1-(bromomethyl)-4-phenoxybenzene (191 mg, 726 μmol) and the mixture was stirred at 140° C. for 50 min under microwave irradiation then at 160° C. for 50 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (10 mL) before extraction with EtOAc (50 mL). The organic phase was isolated and the aqueous phase was further extracted with CH2Cl2 (50 mL). Both organic phases were washed with brine (10 mL), combined, dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:3) gave 43 mg of 6,7-dimethoxy-1-methyl-4-(4-phenoxybenzyl)isoquinolin-3-ol. This free base was dissolved in MeOH (2 mL) in a 10 mL round-bottomed flask equipped with a magnetic stirrer before addition of a 0.09 M HCl solution in MeOH (3 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-1-methyl-4-(4-phenoxybenzyl)isoquinolin-3-ol hydrochloride 5 as a brown solid (47 mg, 15% yield).

Workup

  1. customat 160° C. for 50 min under microwave irradiation
  2. temperatureAfter cooling to RT
  3. customThe organic phase was isolated
  4. extractionthe aqueous phase was further extracted with CH2Cl2 (50 mL)
  5. washBoth organic phases were washed with brine (10 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated at 40° C. under vacuum
  9. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 95:3)

Sources & evidence

ORD record
ord-78c4ae7ca88142698805c1778388baa6
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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