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

HRID 322116Notes

Reaction equation

HRID 322116 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

2-(Furan-3-yl)-1,4-dihydro-5-methoxycarbonyl-6-methyl-4-(4-nitrophenyl)-3-(N-(3-(4,4-diphenylpiperidin-1-yl)propyl)carboxamidopyridine, Hydrochloride Salt (43). 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 1N 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 amine-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 1N 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 amine-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-10acc7dc86b84f12a523c5bc74ac4521
Source dataset
uspto-grants-2001_04
Patent number
US06211198B1

Reaction notes

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