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

HRID 430836Notes

Reaction equation

HRID 430836 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(=O)([O-])[O-].[Li+].[Li+].[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[C:25]([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:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 7412Benzoyl chlorideHCID 11125Lithium CarbonateHCID 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 82.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

N-Methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (52 g, 216 mmol), lithium carbonate (24 g, 325 mmol, 1.5 equivalents), and toluene (155 mL) were heated to a reflux temperature of 100° C. to 105° C. Benzoyl chloride (37.5 g, 267 mmol, 1.25 equivalents) was added, and the entire reaction mixture was allowed to reflux for an additional 6 hours to 8 hours. Once the reaction was complete, the mixture was cooled to 70° C. to 80° C., lithium carbonate was filtered off and the filter cake washed with 100 mL warm toluene, and the combined filtrate and washings were seeded with a few crystals of 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide. Hexane (100 mL) was added to the warm toluene solution to effect crystallization, and the mixture was stirred for 30 minutes; then another 80 mL of hexane was added. The mixture was stirred for 1 hour to 2 hours at room temperature, cooled to 0° C. to 5° C., filtered, washed with hexane (150 mL) and dried under vacuum at 60° C. to 70° C. to yield 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide (61.7 g, 82.8% yield).

Workup

  1. customthe entire reaction mixture
  2. temperatureto reflux for an additional 6 hours to 8 hours
  3. temperaturethe mixture was cooled to 70° C. to 80° C.
  4. filtrationlithium carbonate was filtered off
  5. washthe filter cake washed with 100 mL
  6. temperaturewarm toluene
  7. additionHexane (100 mL) was added to the warm toluene solution to effect crystallization
  8. additionthen another 80 mL of hexane was added
  9. stirringThe mixture was stirred for 1 hour to 2 hours at room temperature
  10. temperaturecooled to 0° C. to 5° C.
  11. filtrationfiltered
  12. washwashed with hexane (150 mL)
  13. customdried under vacuum at 60° C. to 70° C.

Sources & evidence

ORD record
ord-c038cc8e5a8c4cc4839c64ec2b666c84
Source dataset
uspto-grants-2001_11
Patent number
US06323344B1

Reaction notes

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