Imidazole → 1,2,3,4-Tetrahydro-2-[7-[3-[2-(1H-imidazol-1-yl)-ethoxy]-4-methoxyphenyl]-7-[(4-methylphenyl)thio]-heptyl]-6,7-dimethoxyisoquinoline

HRID 274009

Reaction equation

HRID 274009 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].[I-].[Na+].Cl[CH2:11][CH2:12][O:13][C:14]1[CH:15]=[C:16]([CH:22]([S:43][C:44]2[CH:49]=[CH:48][C:47]([CH3:50])=[CH:46][CH:45]=2)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][N:29]2[CH2:38][CH2:37][C:36]3[C:31](=[CH:32][C:33]([O:41][CH3:42])=[C:34]([O:39][CH3:40])[CH:35]=3)[CH2:30]2)[CH:17]=[CH:18][C:19]=1[O:20][CH3:21].[Si]([O-])([O-])([O-])[O-].[Mg+2].[Mg+2]>CN(C)C=O.C(OCC)(=O)C>[N:1]1([CH2:11][CH2:12][O:13][C:14]2[CH:15]=[C:16]([CH:22]([S:43][C:44]3[CH:45]=[CH:46][C:47]([CH3:50])=[CH:48][CH:49]=3)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:38][CH2:37][C:36]4[C:31](=[CH:32][C:33]([O:41][CH3:42])=[C:34]([O:39][CH3:40])[CH:35]=4)[CH2:30]3)[CH:17]=[CH:18][C:19]=2[O:20][CH3:21])[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

8

Reactant 5

HCID 795ImidazoleHCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 66225Magnesium orthosilicateHCID 107698442-[7-[3-(2-Chloroethoxy)-4-methoxyphenyl)-7-[(4-methylphenyl)thio]heptyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline

Product 1

HCID 108416971,2,3,4-Tetrahydro-2-[7-[3-[2-(1H-imidazol-1-yl)-ethoxy]-4-methoxyphenyl]-7-[(4-methylphenyl)thio]-heptyl]-6,7-dimethoxyisoquinolineYield 16,452%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

To 0.76 g of imidazole in 5 mL of 4A sieve-dried N,N-dimethylformamide is added 0.18 g of 60% sodium hydride in oil. When the effervescence subsides, 0.26 g of sodium iodide is added, followed by 1.12 g of 2-[7-[3-(2-chloroethoxy)-4-methoxyphenyl]-7[(4-methylphenyl)thio]heptyl]-1,2,3,4-tetrahydro-6,7dimethoxyisoquinoline in 5 mL of N,N-dimethylformamide. An additional 2 mL of N,N-dimethylformamide is used as wash. After letting the tan solution stand for 48 hours, it is concentrated in vacuo, and the residue is distributed between ethyl acetate and water. The organic layer is extracted with 1N hydrochloric acid, the acid layer basified with aqueous ammonia, and the resulting oil extracted into ethyl acetate. After drying (sodium sulfate), the extract is concentrated in vacuo to 0.53 g of tan oil. Flash chromatography of the oil on silica gel (gradient elution: hexane to chloroform to methyl alcohol) gives an oil which is taken up in ethyl acetate, passed through a pad of hydrous magnesium silicate, and concentrated to leave 0,194 g of the desired product as a yellow gum.

Workup

  1. washas wash
  2. customfor 48 hours
  3. concentrationit is concentrated in vacuo
  4. extractionThe organic layer is extracted with 1N hydrochloric acid
  5. extractionthe resulting oil extracted into ethyl acetate
  6. dry with materialAfter drying (sodium sulfate)
  7. concentrationthe extract is concentrated in vacuo to 0.53 g of tan oil
  8. customFlash chromatography of the oil on silica gel (gradient elution: hexane to chloroform to methyl alcohol) gives an oil which
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-2524cec6c61640198916ce54ba40f2eb
Source dataset
uspto-grants-1995_02
Patent number
US05387685

Linked notes

Loading…