Dichloromethane → 1-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-2-oxo-ethyl]amide

HRID 2288962Notes

Reaction equation

HRID 2288962 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][CH:7]([C:10]([OH:12])=O)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].C(Cl)Cl.C(C1NC=CN=1)(C1NC=CN=1)=O.Cl.[NH2:29][CH2:30][C:31]([C:33]1[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=1)=[O:32]>CN(C=O)C>[F:39][C:36]1[CH:35]=[CH:34][C:33]([C:31](=[O:32])[CH2:30][NH:29][C:10]([CH:7]2[CH2:6][CH2:5][N:4]([C:1](=[O:3])[CH3:2])[CH2:9][CH2:8]2)=[O:12])=[CH:38][CH:37]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 1172551-Acetylpiperidine-4-carboxylic acidHCID 5250894Bis-(1H-imidazol-2-YL)-methanoneHCID 132906662-Amino-1-(4-fluorophenyl)ethan-1-one hydrochloride

Product 1

HCID 187004221-Acetyl-piperidine-4-carboxylic acid [2-(4-fluoro-phenyl)-2-oxo-ethyl]amideYield 85.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a 22-L flask is added 526.4 g (3.07 mol) of 1-acetylpiperidine-4-carboxylic acid, 8 L of methylene chloride, and 55 mL of DMF. To the resultant heterogeneous suspension is added 508.9 g (3.13 mol) of carbonyl diimidazole in two portions at room temperature. After two hours, 583.5 g (3.07 mol) of 2-Amino-1-(4-fluoro-phenyl)-ethanone hydrochloride (J. Heterocylcic Chem (1987), 24, 297. ) is added and the resultant mixture is allowed to stir overnight. The reaction mixture is extracted with 2 N HCl (3×1 L), saturated sodium bicarbonate solution (3×1 L), brine (1×1 L), dried over sodium sulfate, and filtered. To the filtrate is added toluene and the solution is concentrated in-vacuo to ca. 100 mL and the resultant precipitate is filtered. The solid is dried in-vacuo at 60° C. for 18 h to give 800 g of 1-Acetyl-piperidine-4-carboxylic acid[2-(4-fluoro-phenyl)-2-oxo-ethyl]-amide as an off-white solid.

Workup

  1. extractionThe reaction mixture is extracted with 2 N HCl (3×1 L), saturated sodium bicarbonate solution (3×1 L), brine (1×1 L)
  2. dry with materialdried over sodium sulfate
  3. filtrationfiltered
  4. additionTo the filtrate is added toluene
  5. concentrationthe solution is concentrated in-vacuo to ca. 100 mL
  6. filtrationthe resultant precipitate is filtered
  7. customThe solid is dried in-vacuo at 60° C. for 18 h

Sources & evidence

ORD record
ord-c37e51dfbb7e490985b334fa01c8a218
Source dataset
uspto-grants-2000_07
Patent number
US06090825

Reaction notes

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