Hydrochloric Acid → 1-acetyl-N-methoxy-N-methylpiperidine-4-carboxamide

HRID 911083Notes

Reaction equation

HRID 911083 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].N1(C(N2C=CN=C2)=O)C=CN=C1.Cl.[CH3:26][O:27][NH:28][CH3:29].Cl>ClCCl.O1CCOCC1>[C:1]([N:4]1[CH2:5][CH2:6][CH:7]([C:10]([N:28]([O:27][CH3:26])[CH3:29])=[O:12])[CH2:8][CH2:9]1)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 1172551-Acetylpiperidine-4-carboxylic acid

Product 1

HCID 187135481-acetyl-N-methoxy-N-methylpiperidine-4-carboxamideYield 80.72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 1-acetylpiperidine-4-carboxylic acid (58.50 g, 341.7 mmol) in dichloromethane (700 ml) was added di(1H-imidazol-1-yl)methanone (58.18 g, 358.8 mmol) in portions. The mixture was agitated for two hours and N-methoxymethanamine hydrochloride (35.00 g, 358.8 mmol) was added at once. The mixture was stirred overnight at ambient temperature, and then 4M HCl in dioxane (75 ml) was added slowly. The slurry was agitated for 30 minutes and then filtered. The filtrate was washed twice with sodium bicarbonate solution, dried and concentrated in vacuo to give the desired product (59.10 g, 80.72% yield) as a white solid.

Workup

  1. stirringThe mixture was stirred overnight at ambient temperature
  2. stirringThe slurry was agitated for 30 minutes
  3. filtrationfiltered
  4. washThe filtrate was washed twice with sodium bicarbonate solution
  5. customdried
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-575a6781e96449cab8fcffada7216d00
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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