HCID 178418361, compound → HCID 178500115, compound

HRID 2065801Notes

Reaction equation

HRID 2065801 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][C:12]([C:14]([CH3:20])([CH3:19])[C:15]([O:17][CH3:18])=[O:16])=[N:11][C:10]=1[C:21]1[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[C:23]([OH:30])[N:22]=1.[H][H]>[Pd].CO>[NH2:27][C:24]1[CH:25]=[CH:26][C:21]([C:10]2[N:11]=[C:12]([C:14]([CH3:20])([CH3:19])[C:15]([O:17][CH3:18])=[O:16])[NH:13][C:9]=2[C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])=[N:22][C:23]=1[OH:30]

Participants

5

Reactant 2

HCID 178418361HCID 178418361, compoundHCID 178500118HCID 178500118, compound

Product 1

HCID 178500115HCID 178500115, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
55 °C

Procedure

Methyl 2-[5-(2,4-difluorophenyl)-4-(6-hydroxy-5-nitro-2-pyridyl)-1H-imidazol-2-yl]-2-methyl-propanoate (90.0 g, 0.22 mol), wet 10% Pd/C (4.5 g), and methanol (1.77 L) are combined at 15-25° C. The reaction is stirred under 20-25 psig hydrogen atmosphere for 3-6 h. The reaction mixture is filtered over diatomaceous earth, and the filter aid is washed with methanol (227 mL). The filtrate is concentrated under reduced pressure below 40° C., and methyl tert-butyl ether (729.3 mL) is added. The MTBE is removed under reduced pressure below 40° C., and more methyl tert-butyl ether (729.3 mL) is added. The MTBE is removed under reduced pressure below 40° C. Methyl tert-butyl ether (182 mL) and methanol (46 mL) are added and the mixture heated to 50-60° C. for 1-2 h. The mixture is cooled to 10-15° C., and stirred for 2-4 h. The solids are collected by filtration and the filtercake washed with methyl tert-butyl ether (61 mL). The solids are dried under vacuum below 50° C. to furnish the title compound as a yellow solid (75.0 g, 88%).

Workup

  1. customare combined at 15-25° C
  2. filtrationThe reaction mixture is filtered over diatomaceous earth
  3. washthe filter aid is washed with methanol (227 mL)
  4. concentrationThe filtrate is concentrated under reduced pressure below 40° C., and methyl tert-butyl ether (729.3 mL)
  5. additionis added
  6. customThe MTBE is removed under reduced pressure below 40° C., and more methyl tert-butyl ether (729.3 mL)
  7. additionis added
  8. customThe MTBE is removed under reduced pressure below 40° C
  9. additionMethyl tert-butyl ether (182 mL) and methanol (46 mL) are added
  10. temperatureThe mixture is cooled to 10-15° C.
  11. filtrationThe solids are collected by filtration
  12. washthe filtercake washed with methyl tert-butyl ether (61 mL)
  13. customThe solids are dried under vacuum below 50° C.

Sources & evidence

ORD record
ord-f91282f2b0444ea18ee47579209e2d8d
Source dataset
uspto-grants-2012_10
Patent number
US08288548B2

Reaction notes

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