Ammonium Chloride → HCID 178482463, compound

HRID 1620586Notes

Reaction equation

HRID 1620586 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:11][CH2:10][CH:9]([CH:12]=O)[CH2:8][CH2:7]1.[NH:24]=[C:25]1[CH2:29][N:28]([CH3:30])[C:27](=[O:31])[N:26]1C(C1C=CC=CC=1)=O.[CH3:40]C(C)([O-])C.[K+].[Cl-].[NH4+]>C(O)C>[F:22][C:2]([F:23])([F:1])[C:3]1[CH:17]=[C:16]([C:18]([F:21])([F:19])[F:20])[CH:15]=[CH:14][C:4]=1[CH2:5][N:6]1[CH2:7][CH2:8][CH:9](/[CH:12]=[C:29]2\[C:25]([NH:24][CH3:40])=[N:26][C:27](=[O:31])[N:28]\2[CH3:30])[CH2:10][CH2:11]1

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 23665647Potassium tert-butoxideHCID 67504117HCID 67504117, compoundHCID 866786631-[2,4-Bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde

Product 1

HCID 178482463HCID 178482463, compoundYield 0.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-[2,4-bis(trifluoromethyl)benzyl]piperidine-4-carbaldehyde (26.0 g) in ethanol (100 mL) were added 4-imino-1-methyl-3-(phenylcarbonyl)imidazolidin-2-one (16.7 g) and potassium tert-butoxide (8.60 g) under ice-cooling. The reaction mixture was stirred at 80° C. for 2 hr. To the reaction mixture was added saturated aqueous ammonium chloride solution at room temperature, and ethanol was evaporated under reduced pressure. Water and ethyl acetate were added to the residue, and the insoluble material was collected by filtration. The obtained solid was recrystallized from water/ethanol and further recrystallized from water/acetone for purification. To a solution of the obtained solid (2.03 g) in toluene (10 mL) was added a solution (4.8 mL) of methylamine in 40% methanol at room temperature. The reaction mixture was stirred at 70° C. overnight, a solution (4.8 mL) of methylamine in 40% methanol was added at room temperature, and the mixture was stirred at 70° C. overnight. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate) and recrystallized from heptane to give the title compound (223 mg).

Workup

  1. temperaturecooling
  2. customethanol was evaporated under reduced pressure
  3. additionWater and ethyl acetate were added to the residue
  4. filtrationthe insoluble material was collected by filtration
  5. customThe obtained solid was recrystallized from water/ethanol
  6. customfurther recrystallized from water/acetone for purification
  7. additionTo a solution of the obtained solid (2.03 g) in toluene (10 mL) was added a solution (4.8 mL) of methylamine in 40% methanol at room temperature
  8. stirringThe reaction mixture was stirred at 70° C. overnight
  9. additiona solution (4.8 mL) of methylamine in 40% methanol was added at room temperature
  10. stirringthe mixture was stirred at 70° C. overnight
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography (NH, methanol/ethyl acetate)
  13. customrecrystallized from heptane

Sources & evidence

ORD record
ord-5b27fa36c8ab4398ae323c65dcead25c
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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