Chloroacetyl chloride → 1-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-2-chloro-ethanone

HRID 31516Notes

Reaction equation

HRID 31516 reaction equation
Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C:21]([N:23]3[CH2:28][CH2:27][N:26](CCC#N)[CH2:25][CH2:24]3)=[O:22])[C:11]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:42])([F:41])[F:40])=[CH:35][C:34]=3[O:43][CH2:44][CH3:45])=[N:10]2)=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.[Cl:55][CH2:56][C:57](Cl)=[O:58]>C(Cl)Cl>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C:21]([N:23]3[CH2:28][CH2:27][N:26]([C:57](=[O:58])[CH2:56][Cl:55])[CH2:25][CH2:24]3)=[O:22])[C:11]([C:33]3[CH:38]=[CH:37][C:36]([C:39]([F:41])([F:40])[F:42])=[CH:35][C:34]=3[O:43][CH2:44][CH3:45])=[N:10]2)=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 111814993-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-propionitrile hydrochloride

Product 1

HCID 865955291-{4-[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-2-chloro-ethanoneYield 46%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-piperazin-1-yl-methanone (372 mg, 0.63 mmol, example 8A) and diisopropylethylamine (230 uL, 1.32 mmol) were dissolved in methylene chloride (4 mL) and cooled to ice temperature. Chloroacetyl chloride (100 uL, 1.26 mmol) in methylene chloride (1 mL) was added dropwise and this mixture was stirred for 30 min at ice temperature. The reaction was diluted with methylene chloride and washed with water. The organic layers were dried over anhydrous magnesium sulfate. The solids were filtered off, and the filtrate was concentrated. Purification of the crude material by flash chromatography using ethyl acetate and hexanes gave 1-{4-[4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-2-chloro-ethanone (193 mg, 0.29 mmol).

Workup

  1. temperaturecooled to ice temperature
  2. washwashed with water
  3. dry with materialThe organic layers were dried over anhydrous magnesium sulfate
  4. filtrationThe solids were filtered off
  5. concentrationthe filtrate was concentrated
  6. customPurification of the crude material by flash chromatography

Sources & evidence

ORD record
ord-77b772cb48e845a3bde1a11604f1419e
Source dataset
uspto-grants-2008_09
Patent number
US07425638B2

Reaction notes

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