Piperidine → 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide

HRID 1531412Notes

Reaction equation

HRID 1531412 reaction equation
[CH3:1][N:2]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:3]([CH:5]1[C:12]2[N:8]([CH:9]=[CH:10][CH:11]=2)[CH2:7][CH2:6]1)=[O:4].[C:19](N1CCCCC1)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.P(Cl)(Cl)(Cl)=O.[OH-].[Na+].N1CCCCC1>O.C1(C)C=CC=CC=1>[C:19]([C:9]1[N:8]2[C:12](=[CH:11][CH:10]=1)[CH:5]([C:3]([N:2]([CH3:1])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:4])[CH2:6][CH2:7]2)(=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 5

HCID 8082PiperidineHCID 14798Sodium Hydroxide2×HCID 24813Phosphorus oxychlorideHCID 69892BenzoylpiperidineHCID 11299444N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide

Product 1

HCID 98410725-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamideYield 83.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 1140TolueneSolvent3×

Conditions

Temperature
25 °C

Procedure

N-Methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (115.35 g, 480 mmol) and toluene (100 mL) were added to a mixture of benzoylpiperidine (95.4 g, 1.05 equivalents) and phosphorus oxychloride (88 mL, 147 g, 0.96 equivalents), which had been stirred at 25° C. for 1 hour. An additional 100 mL toluene was added. The suspension was heated to a temperature of 40° C. to 45° C. for 4 hours. The resulting syrup was transferred into a rapidly stirring solution of sodium hydroxide (180 g, 4.5 mol), piperidine (1.0 mL), and water (650 mL). The temperature was maintained at 25° C. to 35° C. and the mixture was stirred for 1 hour. A mixture of toluene (100 mL), water (50 mL), and sodium hydroxide (12 g, 300 mmol) was added to the reaction flask, and the entire reaction mixture was stirred at 25° C. for 1 hour. The suspension was then heated to 75° C. and the layers were separated. The organic layer was cooled to 60° C. and hexane (100 mL) was slowly added, and the solution slowly stirred and cooled to −15° C. The precipitate was filtered, washed with toluene/hexane (150 mL, 2:1 v/v) and then with hexane (150 mL), and dried under vacuum at 25° C. to yield 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (138.01 g, 83.5% yield).

Workup

  1. temperatureThe suspension was heated to a temperature of 40° C. to 45° C. for 4 hours
  2. temperatureThe temperature was maintained at 25° C. to 35° C.
  3. stirringthe mixture was stirred for 1 hour
  4. additionwas added to the reaction flask
  5. customthe entire reaction mixture
  6. stirringwas stirred at 25° C. for 1 hour
  7. temperatureThe suspension was then heated to 75° C.
  8. customthe layers were separated
  9. temperatureThe organic layer was cooled to 60° C.
  10. additionhexane (100 mL) was slowly added
  11. stirringthe solution slowly stirred
  12. temperaturecooled to −15° C
  13. filtrationThe precipitate was filtered
  14. washwashed with toluene/hexane (150 mL, 2:1 v/v)
  15. dry with materialwith hexane (150 mL), and dried under vacuum at 25° C.

Sources & evidence

ORD record
ord-21a64cfde2c747db934e779d9c7eacac
Source dataset
uspto-grants-2001_03
Patent number
US06197976B1

Reaction notes

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