Imidazole → 6-[(2RS,4SR)-2-(4-chlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyloxy]-2-[3-(4-chlorophenyl)-propyl]-1,2,3,4-tetrahydroisoquinoline

HRID 2413489Notes

Reaction equation

HRID 2413489 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][N:9]([CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=1)[CH2:8][CH2:7]2.[H][H].CS(O[CH2:31][CH:32]1[CH2:36][O:35][C:34]([C:39]2[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=2)([CH2:37]Br)[O:33]1)(=O)=O.[Na].[NH:47]1[CH:51]=[CH:50][N:49]=[CH:48]1.[I-].[K+]>CC(N(C)C)=O>[Cl:45][C:42]1[CH:41]=[CH:40][C:39]([C:34]2([CH2:37][N:47]3[CH:51]=[CH:50][N:49]=[CH:48]3)[O:33][CH:32]([CH2:31][O:3][C:4]3[CH:5]=[C:6]4[C:11](=[CH:12][CH:13]=3)[CH2:10][N:9]([CH2:14][CH2:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)[CH2:8][CH2:7]4)[CH2:36][O:35]2)=[CH:44][CH:43]=1

Participants

9

Reactant 7

HCID 795ImidazoleHCID 4875Potassium IodideHCID 24758Sodium hydrideHCID 5360545SodiumHCID 133618376-Hydroxy-2-[3-(4-chlorophenyl)propyl]-1,2,3,4-tetrahydroisoquinolineHCID 155764512-Bromomethyl-2-(4-chlorophenyl)-1,3-dioxolan-4-ylmethyl methanesulfonateHCID 178418361HCID 178418361, compound

Product 1

HCID 133619066-[(2RS,4SR)-2-(4-chlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyloxy]-2-[3-(4-chlorophenyl)-propyl]-1,2,3,4-tetrahydroisoquinoline

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

550 mg of sodium hydride (50% suspension in oil) are added to a solution of 3.0 g of 6-hydroxy-2-[3-(4-chlorophenyl)propyl]-1,2,3,4-tetrahydroisoquinoline in 30 ml of dimethylacetamide, the mixture is stirred until evolution of hydrogen has ended, and 3.9 g of (2RS,4SR)-2-(4-chlorophenyl)-2-bromomethyl-1,3-dioxolan-4-ylmethyl methanesulfonate are added. The mixture is heated at 80° for 6 hours, and then 0.9 g of the sodium salt of imidazole and a spatula tip of potassium iodide are added. The solution is stirred at 100° for a further 6 hours. After cooling, the solvent is removed under oil pump vacuum, the residue is taken up with water/methylene chloride, and the organic phase is washed twice with water and dried over magnesium sulfate and the solvent is removed in vacuo. The crude product is purified by chromatography on silica gel using a mixture of ethyl acetate/methanol 9:1. 1.8 g of a viscous oil (31% of theory) which crystallizes on trituration with diethyl ether are obtained. Melting point: 101°-103°.

Workup

  1. temperatureThe mixture is heated at 80° for 6 hours
  2. temperatureAfter cooling
  3. customthe solvent is removed under oil pump vacuum
  4. washthe organic phase is washed twice with water
  5. dry with materialdried over magnesium sulfate
  6. customthe solvent is removed in vacuo
  7. customThe crude product is purified by chromatography on silica gel using
  8. additiona mixture of ethyl acetate/methanol 9:1
  9. custom1.8 g of a viscous oil (31% of theory) which crystallizes on trituration with diethyl ether
  10. customare obtained

Sources & evidence

ORD record
ord-fdebbf9d6c944fee805ad2611ab13e0c
Source dataset
uspto-grants-1988_01
Patent number
US04717724

Reaction notes

Loading…