Acetyl chloride → 2-(4-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine trihydrochloride

HRID 1685217Notes

Reaction equation

HRID 1685217 reaction equation
C([Cl:4])(=O)C.C(OC([N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[N:19]([CH2:34][CH2:35][N:36]([CH3:38])[CH3:37])[CH:20]=[C:21]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[C:25]([C:30]([F:33])([F:32])[F:31])[CH:24]=3)[N:22]=2)[CH2:14][CH2:13]1)=O)(C)(C)C>C(O)C>[ClH:4].[ClH:4].[ClH:4].[F:29][C:26]1[CH:27]=[CH:28][C:23]([C:21]2[N:22]=[C:18]([CH:15]3[CH2:16][CH2:17][NH:12][CH2:13][CH2:14]3)[N:19]([CH2:34][CH2:35][N:36]([CH3:38])[CH3:37])[CH:20]=2)=[CH:24][C:25]=1[C:30]([F:31])([F:32])[F:33]

Participants

4

Reactant 2

HCID 6367Acetyl chlorideHCID 672648444-(1-(2-(Dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866416212-(4-(4-Fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine trihydrochlorideYield 106.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

In a 1 L 3 neck round bottom flask with a mechanical stirrer, thermocouple and nitrogen inlet charge ethanol (339.2 mL) and cool to −5 to 5° C. Add drop-wise neat acetyl chloride (78.5 g, 1 mol, 5 eq) at a rate to maintain temperature at 0-15° C. Cool the resulting solution to 0-5° C. and stir for 30 minutes. Add 4-(1-(2-(dimethylamino)ethyl)-4-(4-fluoro-3-(trifluoromethyl)phenyl)-1H-imidazol-2-yl)piperidine-1-carboxylic acid tert-butyl ester (96.9 g, 0.2 mol, 1 eq) over 5-10 minutes. Warm the reaction solution to RT (crystallization takes place) and stir the resulting suspension for 20-28 hours at RT. Once the reaction is deemed complete, filter the reaction mixture and wash the solids with ethanol (3×58 mL) then with heptane (2×96.9 mL). Dry solids under vacuum at 35-40° C. to afford the target compound (105.13 g, >100% yield) as a light tan solid. m/z (M+H): 385.2

Workup

  1. temperatureto maintain temperature at 0-15° C
  2. temperatureCool the resulting solution to 0-5° C.
  3. temperatureWarm the reaction solution to RT
  4. custom(crystallization takes place)
  5. stirringstir the resulting suspension for 20-28 hours at RT
  6. filtrationfilter the reaction mixture
  7. washwash the solids with ethanol (3×58 mL)
  8. customDry solids under vacuum at 35-40° C.

Sources & evidence

ORD record
ord-76b09313a1fb44e3a2d5afa45809c16f
Source dataset
uspto-grants-2012_04
Patent number
US08148387B2

Reaction notes

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