Trichloroacetyl isocyanate → 2-Carbamoyloxymethyl-4-(3-chlorophenylthio)-5-isopropyl-1-methylimidazole

HRID 1416013Notes

Reaction equation

HRID 1416013 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8][C:9]2[N:10]=[C:11]([CH2:18][OH:19])[N:12]([CH3:17])[C:13]=2[CH:14]([CH3:16])[CH3:15])[CH:5]=[CH:6][CH:7]=1.ClC(Cl)(Cl)[C:22]([N:24]=C=O)=[O:23].C(=O)([O-])O.[Na+]>O1CCCC1>[C:22]([O:19][CH2:18][C:11]1[N:12]([CH3:17])[C:13]([CH:14]([CH3:16])[CH3:15])=[C:9]([S:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[N:10]=1)(=[O:23])[NH2:24]

Participants

5

Reactant 3

HCID 76400Trichloroacetyl isocyanateHCID 473947{4-[(3-Chlorophenyl)sulfanyl]-1-methyl-5-(propan-2-yl)-1H-imidazol-2-yl}methanolHCID 516892Sodium Bicarbonate

Product 1

HCID 4739682-Carbamoyloxymethyl-4-(3-chlorophenylthio)-5-isopropyl-1-methylimidazoleYield 79.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-40 °C

Procedure

In 5 ml of dry tetrahydrofuran was dissolved 200 mg (0.67 mmol)of [4-(3-chlorophenylthio)-5-isopropyl-1-methyl-1H-imidazol-2-yl]methanol (Compound I-38), and 190 mg (1.0 mmol) of trichloroacetylisocyanate was added to the mixture with cooling at -40° C. After 10 minutes, the mixture was warmed to 0° C., and stirred at the same temperature for 10 minutes To the reaction mixture, ice-water was added, and then, the mixture was neutralized with a saturated aqueous sodium hydrogen carbonate solution, and extracted with ethyl acetate. The organic layer was washed with water and dried over sodium sulfate. The solvent was concentrated under reduced pressure, and to the residue was added 5 ml of methanol, 0.5 ml of water and 0.5 ml of triethylamine. The mixture was stirred at 50° C. for 30 minutes. To the reaction mixture was added water, extracted with methylene chloride, the extract was washed with water and dried over sodium sulfate. The solvent was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (ethyl acetate). The product was recrystallized from ethyl acetate/isopropyl ether to give 180 mg of the target compound (Compound I-59)(yield 79%). mp 145-146° C.

Workup

  1. additionwas added to the mixture
  2. temperaturethe mixture was warmed to 0° C.
  3. additionwas added
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. concentrationThe solvent was concentrated under reduced pressure
  8. additionto the residue was added 5 ml of methanol, 0.5 ml of water and 0.5 ml of triethylamine
  9. additionTo the reaction mixture was added water
  10. extractionextracted with methylene chloride
  11. washthe extract was washed with water
  12. dry with materialdried over sodium sulfate
  13. concentrationThe solvent was concentrated under reduced pressure
  14. customthe residue was purified by silica gel chromatography (ethyl acetate)
  15. customThe product was recrystallized from ethyl acetate/isopropyl ether

Sources & evidence

ORD record
ord-3380f15793a24b2ba08941c49c1db36c
Source dataset
uspto-grants-1999_06
Patent number
US05910506

Reaction notes

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