Methyl 3-(pyridin-3-yl)propanoate → N-[4-(1-diphenylmethylpiperidin-4-yl)-butyl]-3-(pyridin-3-yl)-propionamide

HRID 1178399Notes

Reaction equation

HRID 1178399 reaction equation
CO[C:3](=[O:12])[CH2:4][CH2:5][C:6]1[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=1.[C:13]1([CH:19]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:20]2[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH2:30])[CH2:22][CH2:21]2)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C[O-].[Na+]>CO.C1(C)C=CC=CC=1>[C:13]1([CH:19]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[N:20]2[CH2:25][CH2:24][CH:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:3](=[O:12])[CH2:4][CH2:5][C:6]3[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=3)[CH2:22][CH2:21]2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 3

HCID 10329646Methyl 3-(pyridin-3-yl)propanoateHCID 10942334Sodium MethoxideHCID 110346354-(1-Diphenylmethylpiperidine-4-yl)butylamine

Product 1

HCID 9846838N-[4-(1-diphenylmethylpiperidin-4-yl)-butyl]-3-(pyridin-3-yl)-propionamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
102 °C

Procedure

21.6 g (131 mmol) 3-(3-pyridyl)-propionic acid methyl ester, 35.1 g (109 mmol) 4-(1-diphenylmethyl-piperidin-4-yl)-butylamine and 9.8 g (54.5 mmol) 30% sodium methylate solution in methanol are heated to boiling in 480 ml toluene for five hours. Subsequently, 30 ml of solvent is distilled off, sodium methylate precipitates thereby, and the temperature of the suspension increases under heavy foaming to 102° C. The mixture is cooled to 70-80° C. and extracted twice with 45 ml and 30 ml water. The organic phase is azeotropically dried in a moisture separator and cooled to ca. 0° C. The resulting precipitate is filtered and crystallized from 190 ml toluene. Colorless crystals with an MP of 139° C.; yield 46.3 g (93%).

Workup

  1. distillationSubsequently, 30 ml of solvent is distilled off
  2. customsodium methylate precipitates
  3. temperatureThe mixture is cooled to 70-80° C.
  4. extractionextracted twice with 45 ml and 30 ml water
  5. customThe organic phase is azeotropically dried in a moisture separator
  6. temperaturecooled to ca. 0° C
  7. filtrationThe resulting precipitate is filtered
  8. customcrystallized from 190 ml toluene

Sources & evidence

ORD record
ord-89c350a21c674d2bb7c23358289c6e63
Source dataset
uspto-grants-2007_10
Patent number
US07276524B2

Reaction notes

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