Reaction #80579

Reaction equation

4-chloro-N-[4-(methylsulfonyl)phenyl]benzenecarboximidamide

sodium bicarbonate

2-chloro-4'-fluoroacetophenone

→

2-(4-chlorophenyl) -4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole

Yield 36.3%

Solvents

isopropanol

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   TemperatureAfter heating the reaction mixture at 80°-85° C. for 48 hours
3. 3
   Otherthe solvent was removed
4. 4
   workup.DISSOLUTIONThe residue was redissolved in methylene chloride
5. 5
   Washwashed with aqueous sodium bicarbonate and water
6. 6
   Dryingdried over sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated in vacuo
9. 9
   OtherThe crude product (800 mg) was chromatographed (silica gel, hexane/ethyl acetate, 1/1)

Procedure

To a mixture of 4-chloro-N-[4-(methylsulfonyl)phenyl]benzenecarboximidamide (Example 1, Step 1) (400 mg, 1.29 mmol) and sodium bicarbonate (216 mg, 2.59 mmol) in isopropanol (25 mL), 2-chloro-4'-fluoroacetophenone (670 mg, 3.87 mmol) was added. After heating the reaction mixture at 80°-85° C. for 48 hours, the solvent was removed. The residue was redissolved in methylene chloride and washed with aqueous sodium bicarbonate and water. The organic fractions were combined, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product (800 mg) was chromatographed (silica gel, hexane/ethyl acetate, 1/1) to give 2-(4-chlorophenyl) -4-(4-fluorophenyl)-1-[4-(methylsulfonyl)phenyl]-1H-imidazole (200 mg, 36%) as a pale yellow solid: mp (DSC) 180° C. Anal. Calc'd. for C22H16N2SO2FCl: C, 61.90, H, 3.78, N, 6.56, S, 7.51. Found: C, 61.92, H, 3.74, N, 6.43, S, 7.62.

Source