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

HRID 1280764Notes

Reaction equation

HRID 1280764 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 ml (109 mmol) 4-(1-diphenylmethylpiperidine-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 are distilled; thereby, sodium methylate precipitates and the temperature of the suspension increases to 102° C. under heavy foaming. The mixture is cooled to 70-80° C. and extracted twice with 45 ml and 30 ml of water. The organic phase is azeotropically dried on a moisture separator and cooled to ca. 0° C. The resulting precipitate is filtered off and crystallized from 190 ml toluol. Colorless crystals with a MP of 139° C. were recovered; yield: 46.3 g (93%).

Workup

  1. distillationSubsequently, 30 ml of solvent are distilled
  2. customthereby, sodium methylate precipitates
  3. temperatureThe mixture is cooled to 70-80° C.
  4. extractionextracted twice with 45 ml and 30 ml of water
  5. customThe organic phase is azeotropically dried on a moisture separator
  6. temperaturecooled to ca. 0° C
  7. filtrationThe resulting precipitate is filtered off
  8. customcrystallized from 190 ml toluol
  9. customColorless crystals with a MP of 139° C. were recovered

Sources & evidence

ORD record
ord-eed79f641e81482ea4bb459f255846dd
Source dataset
uspto-grants-2002_09
Patent number
US06451816B1

Reaction notes

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