Sodium Thiosulfate → 2-(2,4-difluorophenyl)-3-iodo-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

HRID 1930078Notes

Reaction equation

HRID 1930078 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:16][CH2:15][CH2:14][N:12]2[CH:13]=1.C1C(=O)N([I:24])C(=O)C1.[O-]S([O-])(=S)=O.[Na+].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:16][CH2:15][CH2:14][N:12]2[C:13]=1[I:24]

Participants

5

Reactant 3

HCID 24477Sodium ThiosulfateHCID 120273N-Iodosuccinimide2×HCID 579298552-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole

Product 1

HCID 579298822-(2,4-difluorophenyl)-3-iodo-6,7-dihydro-5H-pyrrolo[1,2-a]imidazoleYield 62.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
22.5 °C

Procedure

To a stirred solution of 2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole (93.5 g, 425 mmol) in DMF (550 mL), NIS (105 g, 467 mmol) was added portionwise over about 1 h, maintaining the temperature at about 20-25° C. with an ice-water bath. After the final addition, the reaction suspension was stirred for about 2 h. After a total of about 3 h from the start of addition of the NIS, the reaction mixture was poured into ice water (4 L) and was stirred at about 15-20° C. for about 15 min before the addition of a 10% solution of Na2S2O3 (500 mL). The resulting solution was stirred for about 1 h. The tan colored solid was collected by vacuum filtration, washed with water (5×200 mL), and dried overnight at room temperature. The solid was stirred with ether (300 mL), filtered, and washed with additional portions of ether (3×30 mL). This ether trituration process was repeated before the solid was dried in a vacuum oven at about 50-60° C. to give the title compound as a powdery solid (91.4 g, 52%): LC/MS (Table 1, Method h) Rt=1.40 min; MS m/z: 347.0 (M+H)+.

Workup

  1. additionAfter the final addition
  2. stirringThe resulting solution was stirred for about 1 h
  3. filtrationThe tan colored solid was collected by vacuum filtration
  4. washwashed with water (5×200 mL)
  5. customdried overnight at room temperature
  6. stirringThe solid was stirred with ether (300 mL)
  7. filtrationfiltered
  8. washwashed with additional portions of ether (3×30 mL)
  9. customwas dried in a vacuum oven at about 50-60° C.

Sources & evidence

ORD record
ord-a6c1d57184ef41e98a8dc71fec10a6ab
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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