Iodoacetamide → HCID 69930291, compound

HRID 874758Notes

Reaction equation

HRID 874758 reaction equation
[N:1]1[NH:2][CH:3]=[C:4]2[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][C:5]=12.[H-].[Na+].I[CH2:19][C:20]([NH2:22])=[O:21]>C(#N)C>[NH2:22][C:20](=[O:21])[CH2:19][N:2]1[CH:3]=[C:4]2[CH2:8][N:7]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:6][C:5]2=[N:1]1

Participants

5

Reactant 3

HCID 3727IodoacetamideHCID 24758Sodium hydrideHCID 178451520HCID 178451520, compound

Product 1

HCID 69930291HCID 69930291, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 2 L three neck flask fitted with a thermometer, a mechanical stirrer and an addition funnel was charged with a suspension of tert-butyl 2,6-dihydropyrrolo[3,4-c]pyrazole-5(4H)-carboxylate (18.01 g, 86.5 mmol) in anhydrous acetonitrile (1.0 L). Sodium hydride (60% dispersion in oil, 4.15 g, 104 mmol) was added to the suspension in one portion under nitrogen. The reaction was stirred at room temperature for 2 h. The resulting white suspension was then cooled in an ice bath and iodoacetamide (31.95 g, 173 mmol) was added. The ice bath was then removed and the mixture was stirred 18 h at room temperature. The mixture was quenched with water (50 mL) and the solvent was removed under reduced pressure. The residue was partitioned between diluted NaCl (50 mL brine and 100 mL water) and 1.0 L EtOAc. The aqueous layer was extracted with 2×1.0 EtOAc. The organic layers were combined and dried over Na2SO4 and solvent was evaporated under reduced pressure. Crude material was purified on silica gel eluting with 20-50% EtOAc/CH2Cl2 to wash out excess iodoacetamide, and then with 2-10% MeOH/CH2Cl2 to afford a mixture of the two products which were separated on a chiral AD column by eluting with 30% MeOH/CO2 to afford the title compound (less mobile fraction). LC-MS=267.32 [M+1].

Workup

  1. temperatureThe resulting white suspension was then cooled in an ice bath
  2. customThe ice bath was then removed
  3. stirringthe mixture was stirred 18 h at room temperature
  4. customThe mixture was quenched with water (50 mL)
  5. customthe solvent was removed under reduced pressure
  6. customThe residue was partitioned between diluted NaCl (50 mL brine and 100 mL water) and 1.0 L EtOAc
  7. extractionThe aqueous layer was extracted with 2×1.0 EtOAc
  8. dry with materialdried over Na2SO4 and solvent
  9. customwas evaporated under reduced pressure
  10. customCrude material was purified on silica gel eluting with 20-50% EtOAc/CH2Cl2
  11. washto wash out excess iodoacetamide
  12. customwith 2-10% MeOH/CH2Cl2 to afford
  13. additiona mixture of the two products which
  14. customwere separated on a chiral AD column
  15. washby eluting with 30% MeOH/CO2

Sources & evidence

ORD record
ord-209b6e782b7a440c966a2c0fdcb80d99
Source dataset
uspto-grants-2015_03
Patent number
US08980929B2

Reaction notes

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