Ethanol, 2-chloro-, 1-(4-methylbenzenesulfonate) → 2-[7-[3-(2-Chloroethoxy)-4-methoxyphenyl)-7-[(4-methylphenyl)thio]heptyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline

HRID 274008Notes

Reaction equation

HRID 274008 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])[CH2:9][N:8]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]([C:30]1[CH:31]=[CH:32][C:33]([O:37][CH3:38])=[C:34]([OH:36])[CH:35]=1)[S:22][C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=1)[CH2:7][CH2:6]2.S(C1C=CC(C)=CC=1)(O[CH2:43][CH2:44][Cl:45])(=O)=O.[H-].[Na+]>CC(=O)CC>[Cl:45][CH2:44][CH2:43][O:36][C:34]1[CH:35]=[C:30]([CH:21]([S:22][C:23]2[CH:24]=[CH:25][C:26]([CH3:29])=[CH:27][CH:28]=2)[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][N:8]2[CH2:7][CH2:6][C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:9]2)[CH:31]=[CH:32][C:33]=1[O:37][CH3:38]

Participants

5

Reactant 3

HCID 6639Ethanol, 2-chloro-, 1-(4-methylbenzenesulfonate)HCID 24758Sodium hydrideHCID 106024275-[7-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-1-[(4-methylphenyl)thio]heptyl]-2-methoxyphenol

Product 1

HCID 107698442-[7-[3-(2-Chloroethoxy)-4-methoxyphenyl)-7-[(4-methylphenyl)thio]heptyl]-1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

To a stirred solution of 5.57 g of 5-[7-(3,4-dihydro-6,7-dimethoxy-2(1H)-isoquinolinyl)-1-[(4-methylphenyl)thio]heptyl]-2-methoxyphenol and 2.0 mL of 2-chloroethyl tosylate in 50 mL of 2-butanone is added 0.44 g of 60% sodium hydride in oil. The solution is heated to reflux for 48 hours and then cooled to room temperature. The solution is partitioned between chloroform and brine and the organic layer dried. The solvent is removed at reduced pressure and the residue chromatographed on silica gel with a gradient elution going from hexane to chloroform to methyl alcohol. The desired fractions are concentrated, dissolved in diethyl ether and passed through a short hydrous magnesium silicate pad. The solvent is removed at reduced pressure to afford 1.6 g of the desired product as a light tan gum.

Workup

  1. temperatureThe solution is heated
  2. temperatureto reflux for 48 hours
  3. customThe solution is partitioned between chloroform and brine
  4. customthe organic layer dried
  5. customThe solvent is removed at reduced pressure
  6. customthe residue chromatographed on silica gel with a gradient elution
  7. concentrationThe desired fractions are concentrated
  8. dissolutiondissolved in diethyl ether
  9. customThe solvent is removed at reduced pressure

Sources & evidence

ORD record
ord-76fc7d138fbf42fdbb9ac18a36acdb85
Source dataset
uspto-grants-1995_02
Patent number
US05387685

Reaction notes

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