Chloroform → Tert-butyl 4-[(3-chloro-4-fluorobenzoyl)amino]piperidine-1-carboxylate

HRID 1256272Notes

Reaction equation

HRID 1256272 reaction equation
C(Cl)(Cl)Cl.[NH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[F:29])[C:23](Cl)=[O:24].C([O-])(O)=O.[Na+]>CCN(CC)CC>[Cl:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][C:28]=1[F:29])[C:23]([NH:5][CH:6]1[CH2:7][CH2:8][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:10][CH2:11]1)=[O:24]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 516892Sodium BicarbonateHCID 12682914-Amino-1-Boc-piperidineHCID 27365483-Chloro-4-fluorobenzoyl Chloride

Product 1

HCID 67131016Tert-butyl 4-[(3-chloro-4-fluorobenzoyl)amino]piperidine-1-carboxylateYield 99.4%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a CHCl3 (350 mL) solution of tert-butyl 4-aminopiperidine-1-carboxylate (35.0 g), Et3N (122 mL) and 3-chloro-4-fluorobenzoyl chloride (37.1 g) were added under ice cooling and the mixture was stirred at the same temperature for 1.5 hours. To the reaction mixture, a saturated aqueous NaHCO3 solution was added and the solution was extracted three times with CHCl3. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to obtain tert-butyl 4-[(3-chloro-4-fluorobenzoyl)amino]piperidine-1-carboxylate (62.0 g). To an EtOAc (300 mL) suspension of the compound obtained, a 4 M HCl/EtOAc solution (300 mL) was added and the mixture was stirred at room temperature for 4 hours. The reaction mixture was concentrated under reduced pressure and 1 M aqueous NaOH solution (300 mL) was added to the residue and the solution was extracted three times with CHCl3. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure. The residue was suspended in EtOAc/hexane (200 mL, 1/1; v/v) and the mixture was stirred for one hour. The precipitate was filtrated to obtain 3-chloro-4-fluoro-N-piperidin-4-ylbenzamide (37.7 g, a colorless solid).

Workup

  1. extractionthe solution was extracted three times with CHCl3
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ee214906ab384952bf45d6b97d900c8a
Source dataset
uspto-grants-2013_06
Patent number
US08461182B2

Reaction notes

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