Water → 4-(4-Chlorophenyl)-1-(imidazol-1-yl)butan-2-one

HRID 467060Notes

Reaction equation

HRID 467060 reaction equation
C(Cl)(=O)C(Cl)=O.[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][CH:16]([OH:23])[CH2:17][N:18]2[CH:22]=[CH:21][N:20]=[CH:19]2)=[CH:10][CH:9]=1.C(N(CC)CC)C.O>ClCCl.CS(C)=O>[Cl:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][C:16](=[O:23])[CH2:17][N:18]2[CH:22]=[CH:21][N:20]=[CH:19]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 109559944-(4-chlorophenyl)-1-(1H-imidazol-1-yl)-2-butanol

Product 1

HCID 110103354-(4-Chlorophenyl)-1-(imidazol-1-yl)butan-2-oneYield 92.7%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of oxalyl chloride (74.8 g) in dry dichloromethane (1350 mL) at below -70° C. under a nitrogen atmosphere was treated with dry dimethyl sulfoxide (91.5 mL) in methylene chloride (270 mL) dropwise over 15 to 20 minutes while maintaining the temperature of the reaction mixture below -50° C. After an additional 5 minutes a solution of (±)-1-(4-(4-chlorophenyl)-2-hydroxybutyl)imidazole (128.3 g) in a mixture of dimethyl sulfoxide (50 mL) and methylene chloride (200 mL) was added over a period of 20 minutes keeping the reaction mixture at temperatures below -65° C. After a further 15 minutes dry triethylamine (300 mL) was added rapidly and after 15 minutes the reaction mixture was allowed to warm to 0° C. Water (20 mL) was then added to the reaction mixture, the methylene chloride then removed by evaporation and the resulting slurry was then treated with water and filtered. The filter cake was washed well with ice-water, cold ethyl acetate and then dried in air to yield 118.0 g of 4-(4-chlorophenyl)-1-(imidazol-1-yl)butan-2-one. The hydrochloride salt crystallized from methanol/acetone had a melting point of 172.5°-174.0° C.

Workup

  1. temperaturewhile maintaining the temperature of the reaction mixture below -50° C
  2. additionwas added over a period of 20 minutes
  3. customat temperatures below -65° C
  4. customthe methylene chloride then removed by evaporation
  5. additionthe resulting slurry was then treated with water
  6. filtrationfiltered
  7. washThe filter cake was washed well with ice-water, cold ethyl acetate
  8. customdried in air

Sources & evidence

ORD record
ord-f8e8e4a5050946c5a4b14e0ff1eaabc7
Source dataset
uspto-grants-1992_10
Patent number
US05158949

Reaction notes

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