Water → N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide

HRID 430833Notes

Reaction equation

HRID 430833 reaction equation
Cl[CH2:2][CH2:3][CH:4]([C:15]1[NH:16][CH:17]=[CH:18][CH:19]=1)[C:5]([N:7]([CH3:14])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:6].[OH-].[Na+].O>C1(C)C=CC=CC=1.CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-]>[CH3:14][N:7]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:5]([CH:4]1[C:15]2[N:16]([CH:17]=[CH:18][CH:19]=2)[CH2:2][CH2:3]1)=[O:6]

Participants

6

Reactant 3

HCID 962WaterHCID 14798Sodium HydroxideHCID 183521654-chloro-N-methyl-N-phenyl-2-(1H-pyrrol-2-yl)butanamide

Product 1

HCID 11299444N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamideYield 63%

Reagents, catalysts & solvents 2

HCID 21218Trioctylmethylammonium chlorideCatalystHCID 1140TolueneSolvent2×

Conditions

Temperature
85 °C

Procedure

A crude solution of 4-chloro-N-methyl-N-phenyl-2-(2-pyrrolyl)butanamide in toluene from the preceding step was added dropwise at 85° C. over 40 minutes to 1 hour to a stirred suspension of ALIQUAT® 336 (2.01 g, 2 mol % with respect to pyrrolylbutanamide) and granular sodium hydroxide (29.9 g, 750 mmol, 3 equivalents) in toluene (50 mL). After the addition was complete, the suspension was stirred under a nitrogen atmosphere at a temperature of 85° C. for 30 minutes, then cooled to 35° C. Cooled water (200 mL) was rapidly added to the mixture and stirred for 15 minutes at 25° C. The solution was rinsed with water and the layers were separated. The organic layer was washed with water (2×100 mL), then distilled under atmospheric pressure to recover the toluene and water. The resultant solution was cooled to 50° C. and allowed to crystallize after the addition of hexane (2×50 mL) and a seed crystal. The suspension was cooled to 5° C. and stirred for 15 minutes. The resultant precipitate was filtered, washed with 100 mL of hexane, and dried under vacuum at 25° C. to yield approximately 38 g (63%) N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide as a beige solid. This solid was recrystallized from toluene (2-2.5 mL/g) to yield large colorless crystals of N-methyl-N-phenyl-2,3-dihydro-1H-pyrrolizine-1-carboxamide, mp 112° C. to 112.5° C.

Workup

  1. additionAfter the addition
  2. temperaturecooled to 35° C
  3. stirringstirred for 15 minutes at 25° C
  4. washThe solution was rinsed with water
  5. customthe layers were separated
  6. washThe organic layer was washed with water (2×100 mL)
  7. distillationdistilled under atmospheric pressure
  8. customto recover the toluene and water
  9. temperatureThe resultant solution was cooled to 50° C.
  10. customto crystallize
  11. additionafter the addition of hexane (2×50 mL)
  12. temperatureThe suspension was cooled to 5° C.
  13. stirringstirred for 15 minutes
  14. filtrationThe resultant precipitate was filtered
  15. washwashed with 100 mL of hexane
  16. customdried under vacuum at 25° C.

Sources & evidence

ORD record
ord-731bff037a2b415393706443ede45f31
Source dataset
uspto-grants-2001_11
Patent number
US06323344B1

Reaction notes

Loading…