Potassium Carbonate → N-[2-[2-[4-(p-Toluidino)piperidin-1-yl]ethyl]phenyl]cyclohexylacetamide

HRID 2223880Notes

Reaction equation

HRID 2223880 reaction equation
FC(F)(F)C(O)=O.[C:8]1([CH3:21])[CH:13]=[CH:12][C:11]([NH:14][CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]2)=[CH:10][CH:9]=1.Br[CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N+:31]([O-])=O.C(=O)([O-])[O-].[K+].[K+].[CH:40]1([CH2:46][C:47](O)=[O:48])[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(O)(=O)C.CN(C)C1C=CN=CC=1.[C].[Pd].C(OCC)(=O)C.ClCCl>[C:8]1([CH3:21])[CH:9]=[CH:10][C:11]([NH:14][CH:15]2[CH2:20][CH2:19][N:18]([CH2:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[NH:31][C:47](=[O:48])[CH2:46][CH:40]3[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]3)[CH2:17][CH2:16]2)=[CH:12][CH:13]=1

Participants

12

Reactant 5

HCID 11430Potassium CarbonateHCID 21363Cyclohexaneacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 123638782-Nitrophenethyl bromideHCID 23020925HCID 23020925, compound

Product 1

HCID 59714925N-[2-[2-[4-(p-Toluidino)piperidin-1-yl]ethyl]phenyl]cyclohexylacetamideYield 41.7%

Reagents, catalysts & solvents 6

HCID 142844-(Dimethylamino)pyridineCatalystHCID 178418390HCID 178418390, compoundCatalystHCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(p-tolyl)aminopiperidine trifluoroacetate (2.21 g) and (2-bromoethyl)-2-nitrobenzene (3.01 g) dissolved in N,N-dimethylformamide (20 mL) was added potassium carbonate (2.92 g). The solution was stirred under heating at 80° C. for 2 hours. Dichloromethane was added to the reaction solution and the insolubles were filtered off, and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)]to give a yellow oily substance (0.6906 g). This was dissolved in acetic acid (20 mL), to which 10% palladium carbon (0.20 g) was added. The mixture was vigorously stirred at room temperature under hydrogen atmosphere for 1 hour. The catalyst was filtered off and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (90:10:0.5)]to give a brown oily substance (0.5041 g). This substance, cyclohexaneacetic acid (0.35 g), 4-dimethylaminopyridine (0.50 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.62 g) were dissolved in N,N-dimethylformamide (10 mL). The solution was stirred at room temperature for 15 hours. After addition of ethyl acetate, the solution was washed in turn with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried (MgSO4) and the solvent was distilled off under reduced pressure. The resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)]to give the title compound (0.4453 g).

Workup

  1. filtrationthe insolubles were filtered off
  2. distillationthe solvent was distilled off under reduced pressure
  3. customThe resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)]to
  4. customgive a yellow oily substance (0.6906 g)
  5. additionwas added
  6. stirringThe mixture was vigorously stirred at room temperature under hydrogen atmosphere for 1 hour
  7. filtrationThe catalyst was filtered off
  8. distillationthe solvent was distilled off under reduced pressure
  9. customThe resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (90:10:0.5)]to
  10. customgive a brown oily substance (0.5041 g)
  11. stirringThe solution was stirred at room temperature for 15 hours
  12. washthe solution was washed in turn with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  13. dry with materialdried (MgSO4)
  14. distillationthe solvent was distilled off under reduced pressure
  15. customThe resulting residue was purified by chromatography [silica gel, dichloromethane-methanol-aqueous ammonia (95:5:0.3)]to

Sources & evidence

ORD record
ord-ba618096e5a6497bbb4b383a06ade9cd
Source dataset
uspto-grants-2008_05
Patent number
US07375115B2

Reaction notes

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