Triethylamine → N-[1-(3,4-Difluorobenzyl)-piperidinyl]-3-hydrazinocarbonyl-propionamide

HRID 968270Notes

Reaction equation

HRID 968270 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH:9](N)[CH2:8][CH2:7]1.C([N:19](CC)CC)C.C[O:25][C:26](=O)[CH2:27][CH2:28][C:29](Cl)=O.[OH2:33].[NH2:34][NH2:35]>ClCCl.C(O)C.O>[F:1][C:2]1[CH:3]=[C:4]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:5][N:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[NH:19][C:26](=[O:25])[CH2:27][CH2:28][C:29]([NH:34][NH2:35])=[O:33]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 73888Butanoic acid, 4-chloro-4-oxo-, methyl esterHCID 180021391-[(3,4-Difluorophenyl)methyl]piperidin-4-amine

Product 1

HCID 69744306N-[1-(3,4-Difluorobenzyl)-piperidinyl]-3-hydrazinocarbonyl-propionamide

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1-(3,4-difluorobenzyl)-piperidin-4-ylamine (8.7 g; EP-A2-0625507) and triethylamine (7.0 ml) in dichloromethane (200 ml) stirring at ambient temperature was treated with 3-chlorocarbonyl-propionic acid methyl ester (5.2 ml). After stirring for 16 hours, the reaction mixture was washed with brine, the organic layer was dried (MgSO4), and evaporated to leave a white solid. This solid was suspended in ethanol (200 ml), treated with hydrazine hydrate (5 ml) and the resulting mixture was stirred at reflux for 16 hours and then allowed to cool. Water (30 ml) was added to the reaction mixture and the ethanol was evaporated. The aqueous residue was then extracted into dichloromethane (6×50 ml), the combined organics were dried (MgSO4) and evaporated to give the subtitle compound as a white solid. (4.8 g)

Workup

  1. washthe reaction mixture was washed with brine
  2. dry with materialthe organic layer was dried (MgSO4)
  3. customevaporated
  4. customto leave a white solid
  5. stirringthe resulting mixture was stirred
  6. temperatureat reflux for 16 hours
  7. temperatureto cool
  8. customthe ethanol was evaporated
  9. extractionThe aqueous residue was then extracted into dichloromethane (6×50 ml)
  10. dry with materialthe combined organics were dried (MgSO4)
  11. customevaporated

Sources & evidence

ORD record
ord-6a35c06c54a64f2b9cca82b12d5cf558
Source dataset
uspto-grants-2005_10
Patent number
US06958350B2

Reaction notes

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