Diethyl Ether → N-(4-acetamidophenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline hydrochloride

HRID 35232Notes

Reaction equation

HRID 35232 reaction equation
Cl.Cl.[NH2:3][C:4]1[CH:26]=[CH:25][C:7]([CH2:8][CH2:9][N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([O:20][CH3:21])[CH:16]=3)[CH:11]2[CH3:24])=[CH:6][CH:5]=1.C(N(CC)CC)C.[C:34]([Cl:37])(=[O:36])[CH3:35].CCOCC>C(Cl)(Cl)Cl>[ClH:37].[C:34]([NH:3][C:4]1[CH:5]=[CH:6][C:7]([CH2:8][CH2:9][N:10]2[CH2:19][CH2:18][C:17]3[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([O:20][CH3:21])[CH:16]=3)[CH:11]2[CH3:24])=[CH:25][CH:26]=1)(=[O:36])[CH3:35]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6367Acetyl chloride2×HCID 8471Triethylamine2×HCID 3033629Veradoline Hydrochloride

Product 1

HCID 14230307N-(4-acetamidophenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline hydrochlorideYield 31.5%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent2×

Procedure

A stirred suspension of N-(4-aminophenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline dihydrochloride (11.9 g, 0.03 m) in chloroform (300 ml) under nitrogen at 0° C. was treated with triethylamine (3.5 g, 0.035 m) and then after 5 minutes with acetyl chloride (2.75 g, 0.035 m). The mixture was stirred for 1 hour, retreated with 3.5 g triethylamine and 2.75 g acetyl chloride and stirred an additional hour at 0°. Chloroform (50 ml) and then ether (100 ml) were added and the white solid precipitate collected by filtration, 13.9 g. The solid was dissolved in chloroform (250 ml), filtered to remove insoluble salts and the filtrate washed with cold 10% NaOH (200 ml) and cold water (2×200 ml) and dried over MgSO4. The solvent was carefully evaporated under vacuum at 20°. The residue was dissolved in 200 ml CHCl3 /100 ml ether, cooled in an ice-salt bath and slowly acidified with HCl gas. The precipitated solid was collected by filtration and recrystallized as above, filtering under nitrogen to protect the solid product from moisture and vacuum dried at 85° to give 3.8 g of N-(4-acetamidophenethyl)-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline hydrochloride, m.p. 150°-154°.

Workup

  1. stirringstirred an additional hour at 0°
  2. filtrationthe white solid precipitate collected by filtration, 13.9 g
  3. dissolutionThe solid was dissolved in chloroform (250 ml)
  4. filtrationfiltered
  5. customto remove insoluble salts
  6. washthe filtrate washed with cold 10% NaOH (200 ml) and cold water (2×200 ml)
  7. dry with materialdried over MgSO4
  8. customThe solvent was carefully evaporated under vacuum at 20°
  9. dissolutionThe residue was dissolved in 200 ml CHCl3 /100 ml ether
  10. temperaturecooled in an ice-salt bath
  11. filtrationThe precipitated solid was collected by filtration
  12. customrecrystallized as above,
  13. filtrationfiltering under nitrogen
  14. customdried at 85°

Sources & evidence

ORD record
ord-aa241c3c5cdb4f63bcc44d11a709c167
Source dataset
uspto-grants-1988_08
Patent number
US04766131

Reaction notes

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