Hydrochloric Acid → 3-methoxy-N-piperidin-4-ylbenzamide

HRID 1256278Notes

Reaction equation

HRID 1256278 reaction equation
[NH2:1][CH:2]1[CH2:7][CH2:6][N:5](C(OC(C)(C)C)=O)[CH2:4][CH2:3]1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20](Cl)=[O:21].Cl.[OH-].[Na+]>CC(O)C.O.CCN(CC)CC>[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:23]=[CH:24][CH:25]=1)[C:20]([NH:1][CH:2]1[CH2:3][CH2:4][NH:5][CH2:6][CH2:7]1)=[O:21]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 74374m-Anisoyl chlorideHCID 12682914-Amino-1-Boc-piperidine

Product 1

HCID 14451573-methoxy-N-piperidin-4-ylbenzamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8471TriethylamineSolvent

Procedure

Step R1-4: To a solution of tert-butyl 4-aminopiperidine-1-carboxylate (150 g) and Et3N (209 mL) in IPA (1.0 L) was added 3-methoxybenzoyl chloride (102 mL) over 40 minutes under ice cooling. The mixture was stirred at room temperature for 2 hours. After cooling to 0° C., 12 M aqueous HCl (0.5 L) was added to the mixture over 30 minutes and the mixture was stirred at 50° C. for 1 hour. After cooling to 0° C., 12 M aqueous NaOH (0.5 L) and water (0.4 L) were added over 40 minutes to the reaction mixture. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4 and concentrated to obtain 3-methoxy-N-(piperidin-4-yl)benzamide as a light brown solid (160 g).

Workup

  1. temperatureAfter cooling to 0° C.
  2. stirringthe mixture was stirred at 50° C. for 1 hour
  3. temperatureAfter cooling to 0° C.
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-40d63a453cef4425ab26bf658c9c6c4f
Source dataset
uspto-grants-2013_06
Patent number
US08461182B2

Reaction notes

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