Methyl iodide → HCID 60164574, compound

HRID 1620143Notes

Reaction equation

HRID 1620143 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[CH2:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11]([CH3:22])=[N:10][C:9]=1[OH:23].[C:29](=O)([O-])[O-].[Cs+].[Cs+].IC>CN(C=O)C.CCOCC>[CH3:2][O:3][C:4]1[CH:5]=[C:6]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[CH2:7][C:8]1[C:17]2[C:12](=[CH:13][C:14]([O:20][CH3:21])=[C:15]([O:18][CH3:19])[CH:16]=2)[C:11]([CH3:22])=[N:10][C:9]=1[O:23][CH3:29]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 10796Cesium carbonateHCID 178489857HCID 178489857, compound2×

Product 1

HCID 60164574HCID 60164574, compoundYield 53.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 4-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1-methylisoquinolin-3-ol (compound 2 free base, 60 mg, 162 μmol), cesium carbonate (70 mg, 215 μmol) and iodomethane (13 μL, 208 μmol) in dry DMF (2 mL) in a 5 mL microwave vial equipped with a magnetic stirrer was stirred at 90° C. for 22 min under microwave irradiation. After cooling to RT, the mixture was diluted with Et2O (50 mL) before washing with water (10 mL) then with brine (10 mL), drying over Na2SO4, filtration and concentration at 40° C. under vacuum. Purification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 75:25) gave 4-(3,4-dimethoxybenzyl)-3,6,7-trimethoxy-1-methylisoquinoline as a colorless oil (33 mg). 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 0.15 M HCl solution in MeOH (1.5 mL). The reaction mixture was stirred for 5 min at RT and concentrated at 40° C. under vacuum. The solid was then washed with Et2O to afford, after drying, 4-(3,4-dimethoxybenzyl)-3,6,7-trimethoxy-1-methylisoquinoline hydrochloride 3 as a pale brown solid (23 mg, 34% yield).

Workup

  1. customvial equipped with a magnetic stirrer
  2. temperatureAfter cooling to RT
  3. washbefore washing with water (10 mL)
  4. dry with materialwith brine (10 mL), drying over Na2SO4, filtration and concentration at 40° C. under vacuum
  5. customPurification by column chromatography (SiO2, eluent cyclohexane:EtOAc=100:0 to 75:25)

Sources & evidence

ORD record
ord-f7bd474f02e6447fa6f2c1f3b375ab46
Source dataset
uspto-grants-2014_07
Patent number
US08772316B2

Reaction notes

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