Ethanol, 2-chloro-, 1-(4-methylbenzenesulfonate) → 7-(2-Chloroethoxy)-alpha-(cyclohexylthio)-alpha-(3,4-dimethoxyphenyl)-3,4-dihydro-6-methoxy-2(1H)-isoquinolineheptanonitrile

HRID 274022Notes

Reaction equation

HRID 274022 reaction equation
[CH:1]1([S:7][C:8]([C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=2)([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:25][CH2:24][C:23]3[C:18](=[CH:19][C:20]([OH:28])=[C:21]([O:26][CH3:27])[CH:22]=3)[CH2:17]2)[C:9]#[N:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[OH-].[Na+].[Cl:41][CH2:42][CH2:43]OS(C1C=CC(C)=CC=1)(=O)=O>CC(=O)CC>[Cl:41][CH2:42][CH2:43][O:28][C:20]1[CH:19]=[C:18]2[C:23]([CH2:24][CH2:25][N:16]([CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][C:8]([S:7][CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)([C:29]3[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[C:31]([O:37][CH3:38])[CH:30]=3)[C:9]#[N:10])[CH2:17]2)=[CH:22][C:21]=1[O:26][CH3:27]

Participants

5

Reactant 3

HCID 6639Ethanol, 2-chloro-, 1-(4-methylbenzenesulfonate)HCID 14798Sodium HydroxideHCID 10650088alpha-(Cyclohexylthio)-alpha-(3,4-dimethoxyphenyl)-3,4-dihydro-7-hydroxy-6-methoxy-2(1H)-isoquinolineheptanenitrile

Product 1

HCID 105794917-(2-Chloroethoxy)-alpha-(cyclohexylthio)-alpha-(3,4-dimethoxyphenyl)-3,4-dihydro-6-methoxy-2(1H)-isoquinolineheptanonitrile

Reagents, catalysts & solvents 1

HCID 6569Methyl Ethyl KetoneSolvent

Procedure

A mixture, under argon, of 2.0 g of product from Example 114, 15 ml of 1N sodium hydroxide, 5.4 ml of 2-chloroethyl-p-toluene sulfonate and 70 ml of 2-butanone is heated at reflux temperature for 18 hours. The mixture is cooled, concentrated in vacuo and the residue partitioned between ethyl acetate and water. The organic layer is washed with saturated sodium chloride, dried, and concentrated in Vacuo to give an oil. The oil is purified by chromatography (silica gel: methylene chloride, 0.5%, 1.0% and 1.5% methyl alcohol/methylene chloride) to give 1.7 g of the desired product.

Workup

  1. temperatureat reflux temperature for 18 hours
  2. temperatureThe mixture is cooled
  3. concentrationconcentrated in vacuo
  4. customthe residue partitioned between ethyl acetate and water
  5. washThe organic layer is washed with saturated sodium chloride
  6. customdried
  7. concentrationconcentrated in Vacuo
  8. customto give an oil
  9. customThe oil is purified by chromatography (silica gel: methylene chloride, 0.5%, 1.0% and 1.5% methyl alcohol/methylene chloride)

Sources & evidence

ORD record
ord-7a097c936f0d439aaca014a8c66ca933
Source dataset
uspto-grants-1995_02
Patent number
US05387685

Reaction notes

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