Imidazole → Trans-1-[6-(4-chlorobenzyloxy)tetrahydropyran-2-ylmethyl]imidazole

HRID 905054Notes

Reaction equation

HRID 905054 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[Cl:8][C:9]1[CH:34]=[CH:33][C:12]([CH2:13][O:14][C@@H:15]2[O:20][C@@H:19]([CH2:21]OS(C3C=CC(C)=CC=3)(=O)=O)[CH2:18][CH2:17][CH2:16]2)=[CH:11][CH:10]=1>CN(C)C=O>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:13][O:14][C@@H:15]2[O:20][C@@H:19]([CH2:21][N:3]3[CH:7]=[CH:6][N:5]=[CH:4]3)[CH2:18][CH2:17][CH2:16]2)=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 13261931trans-6-(4-Chlorobenzyloxy)-2-tosyloxymethyltetrahydropyran

Product 1

HCID 13261934Trans-1-[6-(4-chlorobenzyloxy)tetrahydropyran-2-ylmethyl]imidazoleYield 89.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A mixture of 0.28 g (12 mmoles) of 50% sodium hydride (i.e. 50% w/w sodium hydride in mineral oil) and 0.817 g (12 mmoles) of imidazole was stirred in 25 ml of dimethylformamide at 80° C. for 30 minutes. The mixture was then left to cool at room temperature, after which there was added a solution of 3.30 g of trans-6-(4-chlorobenzyloxy)-2-tosyloxymethyltetrahydropyran in 5 ml of dimethylformamide, at room temperature, and then the mixture was heated at 80°-85° C. for 2 hours. After cooling the mixture, it was poured into ice-water and then extracted with diethyl ether. The ethereal extract was washed with an aqueous solution of sodium chloride and dried over anhydrous sodium sulphate, after which the solvent was evaporated off. The residue was purified by column chromatography through 50 g of silica gel eluted with a 30:1:1 by volume mixture of ethyl acetate, ethanol and triethylamine, to give 2.21 g of the title compound as a colourless oil.

Workup

  1. waitThe mixture was then left
  2. temperatureat room temperature, and then the mixture was heated at 80°-85° C. for 2 hours
  3. temperatureAfter cooling the mixture, it
  4. extractionextracted with diethyl ether
  5. extractionThe ethereal extract
  6. washwas washed with an aqueous solution of sodium chloride
  7. dry with materialdried over anhydrous sodium sulphate
  8. customafter which the solvent was evaporated off
  9. customThe residue was purified by column chromatography through 50 g of silica gel
  10. washeluted with a 30:1:1 by volume mixture of ethyl acetate, ethanol and triethylamine

Sources & evidence

ORD record
ord-3ab22bd7bf334f09899455defffe9599
Source dataset
uspto-grants-1983_12
Patent number
US04421758

Reaction notes

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