Potassium Hydroxide → HCID 178440233, compound

HRID 1620163Notes

Reaction equation

HRID 1620163 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]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[CH:6]2.[OH-].[K+].Br[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1>C1(C)C=CC=CC=1.O.C(Cl)Cl>[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]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]([OH:18])=[C:6]2[CH2:22][C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=1

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 703202-BromomethylnaphthaleneHCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440233HCID 178440233, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (125 mg, 505 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.30 mL, 0.60 mmol) at RT followed by 2-(bromomethyl)naphthalene (123 mg, 556 μmol) and the mixture was stirred at 150° C. for 45 min under microwave irradiation. After cooling to RT, the mixture was diluted with H2O (10 mL) before extraction with CH2Cl2 (80 mL). The organic phase was isolated and washed with brine (10 mL), dried over Na2SO4, filtered and concentrated at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 97:3) gave 57 mg of 6,7-dimethoxy-4-(naphthalen-2-ylmethyl)-1-propylisoquinolin-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 0.42 M HCl solution in MeOH (4.0 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 6,7-dimethoxy-4-(naphthalen-2-ylmethyl)-1-propylisoquinolin-3-ol hydrochloride 20 as a yellow solid (62 mg, 29% yield).

Workup

  1. temperatureAfter cooling to RT
  2. customThe organic phase was isolated
  3. washwashed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated at 40° C. under vacuum
  7. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 97:3)

Sources & evidence

ORD record
ord-736cdc55f13e4d32835b6b66a5ee6adc
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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