2-Dimethylaminopyridine → 3-(4,4-Diphenylpiperidin-1-yl)propyl 3-oxo-3-(furan-3-yl)propanamide

HRID 382668Notes

Reaction equation

HRID 382668 reaction equation
N[CH2:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][C:8]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7][CH2:6]1.[O:23]=[C:24]([C:31]1[CH:35]=[CH:34][O:33][CH:32]=1)[CH2:25][C:26]([O:28]CC)=O.C[N:37](C1C=CC=CN=1)C>C1(C)C=CC=CC=1.CCOC(C)=O>[C:11]1([C:8]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:7][CH2:6][N:5]([CH2:4][CH2:3][CH2:2][CH:25]([C:24](=[O:23])[C:31]3[CH:35]=[CH:34][O:33][CH:32]=3)[C:26]([NH2:37])=[O:28])[CH2:10][CH2:9]2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

6

Reactant 3

HCID 218852-DimethylaminopyridineHCID 336409Ethyl 3-(furan-3-yl)-3-oxopropanoateHCID 101085183-Amino-propyl-4,4-diphenyl piperidine

Product 1

HCID 865866333-(4,4-Diphenylpiperidin-1-yl)propyl 3-oxo-3-(furan-3-yl)propanamide

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

This compound was initially prepared according to Method A, and later according to Method B (see below). Method A: A stirred solution of 191 mg of 1-(3-aminopropyl)-4,4-diphenylpiperidine (0.676 mmol), 123 mg of ethyl 3-oxo-3-(furan-3-yl)propionate (0.676 mmol), and 83 mg of dimethylaminopyridine (0.676 mmol) in 5 mL of dry toluene were heated at reflux temperature for 18 hrs, cooled, and the residue was dissolved in 30 mL of EtOAc. The resulting solution was extracted with 2×20 mL of aqueous 1 N HCl solution. The combined aqueous extracts were washed with 20 mL of 1:1 EtOAc-ether, basified with NaHCO3 (pH=8-9), and extracted with 2×20 mL of EtOAc. The combined EtOAc extracts were dried (Na2SO4), the solvent was removed in vacuo, and the crude product was chromatographed on 100 g of silica packed with MeOH-isopropyl amine-EtOAc (1:1:98). The column was eluted with MeOH-isopropyl amino-EtOAc 1:1:98, 2:1:97, 5:1:94, 10:1:89, 20:1:79 (0.5 L each) to give N-(3-(4,4-diphenylpiperidin-1-yl)propyl 3-oxo-3-(furan-3-yl)propanamide as a slightly yellow viscous oil. The product was used in the next step after spectral characterization.

Workup

  1. customThis compound was initially prepared
  2. temperatureat reflux temperature for 18 hrs
  3. temperaturecooled
  4. extractionThe resulting solution was extracted with 2×20 mL of aqueous 1 N HCl solution
  5. washThe combined aqueous extracts were washed with 20 mL of 1:1 EtOAc-ether
  6. extractionextracted with 2×20 mL of EtOAc
  7. dry with materialThe combined EtOAc extracts were dried (Na2SO4)
  8. customthe solvent was removed in vacuo
  9. customthe crude product was chromatographed on 100 g of silica
  10. washThe column was eluted with MeOH-isopropyl amino-EtOAc 1:1:98, 2:1:97, 5:1:94, 10:1:89, 20:1:79 (0.5 L each)

Sources & evidence

ORD record
ord-5ae8d529e2c84666883f47a6de82050c
Source dataset
uspto-grants-2001_10
Patent number
US06310076B1

Reaction notes

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