HCID 178418361, compound → HCID 178507215, compound

HRID 1523277Notes

Reaction equation

HRID 1523277 reaction equation
[F:1][C:2]([F:32])([F:31])[O:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:11]=[C:12]([CH2:15][C:16]3([NH:20]C(=O)OCC4C=CC=CC=4)[CH2:19][O:18][CH2:17]3)[NH:13][CH:14]=2)=[CH:6][CH:5]=1.[H][H]>CO.C(OCC)(=O)C>[F:32][C:2]([F:1])([F:31])[O:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[N:11]=[C:12]([CH2:15][C:16]3([NH2:20])[CH2:17][O:18][CH2:19]3)[NH:13][CH:14]=2)=[CH:8][CH:9]=1

Participants

5

Reactant 2

HCID 178418361HCID 178418361, compoundHCID 178521723HCID 178521723, compound

Product 1

HCID 178507215HCID 178507215, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzyl [3-({4-[4-(trifluoromethoxy)phenyl]-1H-imidazol-2-yl}methyl)oxetan-3-yl]-carbamate (Preparation 11, 311 g, 695 mmol) was dissolved in methanol (3.2 L). 5% Palladium on carbon E105 R/W (EVONIK) (22 g, 7 wt %) was added and the reaction hydrogenated at 40° C., 100 psi for 18 hours. Hydrogen uptake was monitored and showed the reaction to be complete after 4 hours. The mixture was cooled to room temperature and filtered over Arbocel©. The filter cake was washed with methanol (2×1 L) and the filtrate concentrated in vacuo to afford a solid. The solid was dissolved in ethyl acetate (1 L) and filtered through a carbon tablet to remove traces of palladium. The solution was warmed to 50° C. and heptane (1 L) added. The solution was cooled slowly whereupon at 40° C. crystallisation was observed. The mixture was stirred at room temperature for 72 hours. The solid was collected by filtration and washed with ethyl acetate: heptane (1:1, 250 mL). The solid was dried in vacuo at 40° C. for 18 hours to afford the title compound as a crystalline solid.

Workup

  1. customthe reaction hydrogenated at 40° C.
  2. customthe reaction
  3. waitto be complete after 4 hours
  4. filtrationfiltered over Arbocel©
  5. washThe filter cake was washed with methanol (2×1 L)
  6. concentrationthe filtrate concentrated in vacuo
  7. customto afford a solid
  8. filtrationfiltered through a carbon tablet
  9. customto remove traces of palladium
  10. temperatureThe solution was warmed to 50° C.
  11. additionheptane (1 L) added
  12. temperatureThe solution was cooled slowly whereupon at 40° C. crystallisation
  13. filtrationThe solid was collected by filtration
  14. washwashed with ethyl acetate: heptane (1:1, 250 mL)
  15. customThe solid was dried in vacuo at 40° C. for 18 hours

Sources & evidence

ORD record
ord-5ef43141dc4145f38c9ed55bfe95b04e
Source dataset
uspto-grants-2015_07
Patent number
US09079878B2

Reaction notes

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