Water → 4,4,4-Trifluorobutane-1-sulfonic acid 4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]-phenyl ester

HRID 1715101Notes

Reaction equation

HRID 1715101 reaction equation
[N:1]1([NH:7][C:8]([C:10]2[N:11]=[C:12]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=3[Cl:30])[N:13]([C:16]3[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=3)[C:14]=2[CH3:15])=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C.[F:38][C:39]([F:48])([F:47])[CH2:40][CH2:41][CH2:42][S:43](Cl)(=[O:45])=[O:44].O>ClCCl>[Cl:30][C:24]1[CH:25]=[C:26]([Cl:29])[CH:27]=[CH:28][C:23]=1[C:12]1[N:13]([C:16]2[CH:17]=[CH:18][C:19]([O:22][S:43]([CH2:42][CH2:41][CH2:40][C:39]([F:48])([F:47])[F:38])(=[O:45])=[O:44])=[CH:20][CH:21]=2)[C:14]([CH3:15])=[C:10]([C:8](=[O:9])[NH:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8471Triethylamine2×HCID 27611764,4,4-trifluorobutane-1-sulfonyl Chloride2×HCID 589650752-(2,4-Dichlorophenyl)-1-(4-hydroxyphenyl)-5-methyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide

Product 1

HCID 116644794,4,4-Trifluorobutane-1-sulfonic acid 4-[2-(2,4-dichlorophenyl)-5-methyl-4-(piperidin-1-ylcarbamoyl)imidazol-1-yl]-phenyl esterYield 61%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-(2,4-Dichlorophenyl)-1-(4-hydroxyphenyl)-5-methyl-1H-imidazole-4-carboxylic piperidin-1-ylamide, from Ex 2, Step 1 (0.49 g, 1.20 mmol) was dissolved in dichloromethane (20 ml), cooled to 0° C. and triethylamine (0.67 ml, 4.8 mmol) added followed by 4,4,4-trifluorobutane-1-sulfonyl chloride (prepared as described in WO00/010968) (0.38 g, 1.80 mmol). The reaction mixture was stirred at room temperature for 3 hrs. TLC showed remaining starting material and another portion of triethylamine and 4,4,4-trifluorobutane-1-sulfonyl chloride was added and the reaction mixture stirred overnight. Water was added, the product extracted with dichloromethane, dried (Na2SO4), filtered and concentrated. Flash chromatography (hexane:EtOAc 1:3-EtOAc) followed by recrystallization (hexane:EtOAc) afforded 0.45 g (61%) of the title compound as a colorless solid.

Workup

  1. customprepared
  2. stirringthe reaction mixture stirred overnight
  3. extractionthe product extracted with dichloromethane
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customFlash chromatography (hexane:EtOAc 1:3-EtOAc) followed by recrystallization (hexane:EtOAc)

Sources & evidence

ORD record
ord-bf5ab2add59e4b3dbfd6bab500706f57
Source dataset
uspto-grants-2010_09
Patent number
US07799804B2

Reaction notes

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