Potassium Hydroxide → HCID 178440235, compound

HRID 1620150Notes

Reaction equation

HRID 1620150 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+].Cl[CH2:22][C:23]1[CH:35]=[CH:34][C:26]2[O:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[C:25]=2[CH:24]=1>C1(C)C=CC=CC=1.C(Cl)Cl>[CH:24]1[C:25]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[O:27][C:26]=2[CH:34]=[CH:35][C:23]=1[CH2:22][C:6]1[C:5]2[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]([CH2:15][CH2:16][CH3:17])=[N:8][C:7]=1[OH:18]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 2337372-(Chloromethyl)dibenzofuranHCID 178440211HCID 178440211, compound2×

Product 1

HCID 178440235HCID 178440235, compoundYield 8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 6,7-dimethoxy-1-propylisoquinolin-3-ol RBO 35142 (75 mg, 303 μmol) in toluene (10 mL) in a 20 mL microwave vial equipped with a magnetic stirrer was added a 2 N aq. KOH solution (0.15 mL, 0.30 mmol) at RT followed by 2-(chloromethyl)dibenzo[b,d]furan CCH 34116-2 (70 mg, 323 μmol) and the mixture was stirred at 150° C. for 1.5 h under microwave irradiation. After cooling to RT, the mixture was diluted with CH2Cl2:MeOH=9:1 (50 mL), 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 96:4) gave, after evaporation and drying, 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol (11 mg, 8% yield). 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 0.20 M HCl solution in MeOH (0.25 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum to afford 4-(dibenzo[b,d]furan-2-ylmethyl)-6,7-dimethoxy-1-propylisoquinolin-3-ol hydrochloride 7 as a pale brown solid (11 mg, 8% yield).

Workup

  1. temperatureAfter cooling to RT
  2. washMeOH=9:1 (50 mL), washed with brine (10 mL)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated at 40° C. under vacuum
  6. customPurification by column chromatography (SiO2, eluent CH2Cl2:MeOH=100:0 to 96:4)
  7. customgave
  8. customafter evaporation
  9. customdrying

Sources & evidence

ORD record
ord-f41090befcf84b5d9773f5a392ba33bd
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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