Hydrochloric Acid → 1H-Imidazole-2-propanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(4-pyridinylmethyl)-

HRID 1857777Notes

Reaction equation

HRID 1857777 reaction equation
C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]([CH2:29][C:30]2[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=2)[C:14]([S:20][C:21]2[CH:26]=[C:25]([Cl:27])[CH:24]=[C:23]([Cl:28])[CH:22]=2)=[C:15]([CH:17]([CH3:19])[CH3:18])[N:16]=1)C1C=CC=CC=1.Cl.C(=O)([O-])O.[Na+]>>[Cl:27][C:25]1[CH:26]=[C:21]([S:20][C:14]2[N:13]([CH2:29][C:30]3[CH:35]=[CH:34][N:33]=[CH:32][CH:31]=3)[C:12]([CH2:11][CH2:10][CH2:9][OH:8])=[N:16][C:15]=2[CH:17]([CH3:19])[CH3:18])[CH:22]=[C:23]([Cl:28])[CH:24]=1

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 22130774HCID 22130774, compound

Product 1

HCID 4740981H-Imidazole-2-propanol, 5-((3,5-dichlorophenyl)thio)-4-(1-methylethyl)-1-(4-pyridinylmethyl)-Yield 76%

Conditions

Temperature
110 °C

Procedure

In 50 ml of tetrahydrofuran was dissolved 5.0 g (11.5 mmol.) of imidazole (101e), followed by addition of 5 ml of water and 1.84 g (46 mmol) of sodium hydroxide, and then, 250 mg (0.8 mmol) of n-tetrabutylammonium bromide and 2.3 g (14 mmol) of 4-chloromethylpyridine hydrochloride were further added. The mixture was stirred under heating at 50° C. for 8 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% methanol-ethyl acetate) to provide 2-(3-benzyloxypropyl)-5-(3,5-dichlorophenylthio)-4-isopropyl-1-(pyridin-4-yl)methyl-1H-imidazole (136c) as oil. To thus-obtained oil (136c) was added 27 ml of concentrated hydrochloric acid and the mixture was heated at 110° C. for 2 hours. After cooling, the mixture was neutralized with sodium hydrogen carbonate and extracted with ethyl acetate. The extract was washed with water, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5% methanol-ethyl acetate) and recrystallized from ethyl acetate-n-hexane to provide 3.8 g (yield 76%) of 3-(5-(3,5-dichlorophenylthio)-4-isopropyl-1-(pyridin-4-ylmethyl)-1H-imidazol-2-yl)-propan-1-ol (137c) as crystals. mp 106-107° C.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (5% methanol-ethyl acetate)
  8. customrecrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-05f9aeaee5c8470f957e848bd35a76f6
Source dataset
uspto-grants-2000_11
Patent number
US06147097

Reaction notes

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