Hydroxylamine → 4-Methyl-5-[4-(trifluoromethyl)phenyl]-1H-imidazol-2-amine

HRID 241435Notes

Reaction equation

HRID 241435 reaction equation
[CH3:1][C:2]1[N:3]=[C:4]2[N:9]=CC=C[N:5]2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1.NO>CCO>[CH3:1][C:2]1[N:3]=[C:4]([NH2:9])[NH:5][C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 787HydroxylamineHCID 710597752-Methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine

Product 1

HCID 1784333994-Methyl-5-[4-(trifluoromethyl)phenyl]-1H-imidazol-2-amineYield 95%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Stir a mixture of 2-methyl-3-[4-(trifluoromethyl)phenyl]imidazo[1,2-a]pyrimidine (180 g, 649.2 mmol, 1 equiv) in EtOH (1.4 L) and hydroxylamine (159 ml, 2.596 mol, 4 equiv) at an internal temperature of 82° C. for 48 hours. Cool the mixture, and concentrate to dryness. Dilute the residue with DCM (1.5 L), and wash sequentially with water (2×500 ml) and brine (500 ml). Dry the organic phase over MgSO4; filter; collect the filtrate and; and remove the solvent in vacuo to give a yellow gum. Purify the resulting material by flash chromatography on silica gel (2 kg), eluting with a gradient of 4:1:0.02 DCM/MeOH/NH3 to obtain the title compound as a yellow foam (95% yield). MS (m/z) 242 (M+1).

Workup

  1. temperatureCool the mixture
  2. concentrationconcentrate to dryness
  3. additionDilute the residue with DCM (1.5 L)
  4. washwash sequentially with water (2×500 ml) and brine (500 ml)
  5. dry with materialDry the organic phase over MgSO4
  6. filtrationfilter
  7. customcollect the filtrate
  8. customand remove the solvent in vacuo
  9. customto give a yellow gum
  10. customPurify the resulting material by flash chromatography on silica gel (2 kg)
  11. washeluting with a gradient of 4:1:0.02 DCM/MeOH/NH3

Sources & evidence

ORD record
ord-9ed8440d7c3c47dc8cf5013c054f3279
Source dataset
uspto-grants-2014_02
Patent number
US08648200B2

Reaction notes

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