Methyl iodide → HCID 19737411, compound

HRID 258337Notes

Reaction equation

HRID 258337 reaction equation
[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([CH2:20][C:21]4[NH:22][CH:23]=[CH:24][N:25]=4)[O:17][CH:16]([CH2:18][OH:19])[CH2:15][O:14]3)=[CH:9][CH:8]=2)=[C:4]([CH3:28])[CH:3]=1.[H-].[Na+].[CH3:31]I>>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][C:10]([C:13]3([CH2:20][C:21]4[NH:25][CH:24]=[CH:23][N:22]=4)[O:17][CH:16]([CH2:18][O:19][CH3:31])[CH2:15][O:14]3)=[CH:9][CH:8]=2)=[C:4]([CH3:28])[CH:3]=1

Participants

4

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67855931HCID 67855931, compound

Product 1

HCID 19737411HCID 19737411, compound

Procedure

16 parts of 2-[p-(4-chloro-2-methylphenoxy)phenyl]-2-(1-imidazolylmethyl)-4-hydroxymethyl-1,3-dioxolane are dissolved in 150 ml of N,,N-dimethyl formamide and then 1.9 parts of 55% sodium hydride dispersion are stirred in while introducing nitrogen. The mixture is heated for 2 hours to 80° C., then cooled to room temperature, treated dropwise, with stirring, with 6.3 parts of methyl iodide over 1 hour, then heated for 2 hours to 60° C., diluted with 800 ml of ice-water and extracted with three 300 ml portions of ethyl acetate. The combined extracts are washed with two 50 ml portions of water, dried over sodium sulfate, filtered, and the solvent is removed by evaporation. The residue is purified by column chromatography over silica gel with acetone/ethyl acetate (1:1). The eluant is then removed by evaporation and the mixture of diastereoisomers is crystallised by treatment with tiexane, giving beige-coloured crystals with a melting point of 92°-106° C.

Workup

  1. additionwhile introducing nitrogen
  2. temperatureThe mixture is heated for 2 hours to 80° C.
  3. additiontreated dropwise
  4. temperatureheated for 2 hours to 60° C.
  5. extractionextracted with three 300 ml portions of ethyl acetate
  6. washThe combined extracts are washed with two 50 ml portions of water
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent is removed by evaporation
  10. customThe residue is purified by column chromatography over silica gel with acetone/ethyl acetate (1:1)
  11. customThe eluant is then removed by evaporation
  12. additionthe mixture of diastereoisomers
  13. customis crystallised by treatment with tiexane
  14. customgiving beige-coloured crystals with a melting point of 92°-106° C.

Sources & evidence

ORD record
ord-85d07873b9d94e48b1637317ad1b3d58
Source dataset
uspto-grants-1993_11
Patent number
US05266585

Reaction notes

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