Water → 2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

HRID 1930077Notes

Reaction equation

HRID 1930077 reaction equation
Br[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:6]=1[F:12])=O.Cl.[NH:14]1[CH2:18][CH2:17][CH2:16][C:15]1=[NH:19].C([O-])([O-])=O.[Na+].[Na+].O>CN(C=O)C>[F:12][C:6]1[CH:7]=[C:8]([F:11])[CH:9]=[CH:10][C:5]=1[C:3]1[N:19]=[C:15]2[CH2:16][CH2:17][CH2:18][N:14]2[CH:2]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27741852-Bromo-2',4'-difluoroacetophenoneHCID 178479085HCID 178479085, compound

Product 1

HCID 579298552-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoleYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-bromo-1-(2,4-difluorophenyl)ethanone (150 g, 640 mmol, Example #8, Step A), pyrrolidin-2-imine hydrochloride (108 g, 894 mmol) and Na2CO3 (134 mL, 3190 mmol) in DMF (650 mL) was stirred and heated at about 80° C. in a 3 L 3 necked flask for about 24 h. The mixture was cooled to ambient temperature and poured into water (about 5 L). The product was partitioned between EtOAc (800 mL) and the basic aqueous phase. The aqueous layer was extracted with additional EtOAc (3×800 mL). The combined organic extracts were washed with water (4×800 mL), dried over MgSO4 and filtered through a pad of Florisil® (2″ depth×3″ diameter). The pad was washed with EtOAc (4×250 mL) and the filtrate was concentrated to dryness under reduced pressure to yield the title compound as a solid (98.6 g, 70%): LC/MS (Table 1, Method a) Rt=2.72 min; MS m/z: 221.0 (M+H)+.

Workup

  1. customThe product was partitioned between EtOAc (800 mL)
  2. extractionThe aqueous layer was extracted with additional EtOAc (3×800 mL)
  3. washThe combined organic extracts were washed with water (4×800 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered through a pad of Florisil® (2″ depth×3″ diameter)
  6. washThe pad was washed with EtOAc (4×250 mL)
  7. concentrationthe filtrate was concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-8c09e2b67da5416695ce3bc27f089c32
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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