Potassium Carbonate → 3-Cyclohexyl-N-[2-[3-[4-(p-toluidino)piperidin-1-yl]propyl]phenyl]propionamide

HRID 2223881Notes

Reaction equation

HRID 2223881 reaction equation
F[C:2](F)(F)[C:3]([OH:5])=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][CH:24]=[CH:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[N+:32]([O-])=O.C(=O)([O-])[O-].[K+].[K+].[CH:41]1([CH2:47]C(O)=O)[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]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>[CH:41]1([CH2:47][CH2:2][C:3]([NH:32][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=2[CH2:25][CH2:24][CH2:23][N:18]2[CH2:19][CH2:20][CH:15]([NH:14][C:11]3[CH:10]=[CH:9][C:8]([CH3:21])=[CH:13][CH:12]=3)[CH2:16][CH2:17]2)=[O:5])[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1

Participants

12

Reactant 5

HCID 11430Potassium CarbonateHCID 21363Cyclohexaneacetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 23020925HCID 23020925, compoundHCID 54507822(3-Bromopropenyl)-2-nitrobenzene

Product 1

HCID 597149043-Cyclohexyl-N-[2-[3-[4-(p-toluidino)piperidin-1-yl]propyl]phenyl]propionamideYield 46.1%

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 (2.08 g) and (3-bromopropenyl)-2-nitrobenzene (3.01 g) dissolved in N,N-dimethylformamide (20 mL) was added potassium carbonate (2.75 g). The solution was stirred with 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 (1.05 g). This was dissolved in acetic acid (25 mL), to which 10% palladium carbon (0.50 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 (0.5443 g). Part of the substance (0.3870 g), cyclohexaneacetic acid (0.28 g), 4-dimethylaminopyridine (0.50 g) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.46 g) were dissolved in N,N-dimethylformamide (5 mL). The solution was stirred at room temperature for 18 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, dichloro-methane-methanol-aqueous ammonia (97:3:0.2)] to give the title compound (0.4190 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)]
  4. customto give a yellow oily substance (1.05 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)]
  10. customto give a brown oily substance (0.5443 g)
  11. stirringThe solution was stirred at room temperature for 18 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, dichloro-methane-methanol-aqueous ammonia (97:3:0.2)]

Sources & evidence

ORD record
ord-755c1f08daaa4913ac74c4a88266bfe2
Source dataset
uspto-grants-2008_05
Patent number
US07375115B2

Reaction notes

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