Acetic Acid → 1-(4-(2-(4-((1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone

HRID 410271Notes

Reaction equation

HRID 410271 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:33]=[CH:32][C:15]([O:16][C:17]2[C:22]([C:23]3[CH2:28][CH2:27][N:26]([C:29](=[O:31])[CH3:30])[CH2:25][CH:24]=3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:14][CH:13]=1)=[O:11].C(O)(=O)C>[Pd].O1CCCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH:10]([OH:11])[C:12]1[CH:13]=[CH:14][C:15]([O:16][C:17]2[C:22]([CH:23]3[CH2:28][CH2:27][N:26]([C:29](=[O:31])[CH3:30])[CH2:25][CH2:24]3)=[CH:21][CH:20]=[CH:19][N:18]=2)=[CH:32][CH:33]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 593269261-(4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone

Product 1

HCID 674179681-(4-(2-(4-((1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

1-(4-(2-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyridin-3-yl)-5,6-dihydropyridin-1(2H)-yl)ethanone (0.42 g, 0.96 mmol), acetic acid, glacial (0.11 mL, 1.92 mmol) and palladium on carbon, 10% (0.20 g, 0.19 mmol) were suspended in tetrahydrofuran (10 mL) in a pressure reactor. The mixture was hydrogenated at 50 psi for 16 h. The catalyst was filtered off and washed with THF. To the solution was added palladium on carbon, 10% (0.204 g, 0.192 mmol) and acetic acid, glacial (0.111 mL, 1.916 mmol) and the mixture was hydrogenated at 50 psi for another 24 h. The mixture was filtered through celite and washed with THF. The solvent was removed under reduced pressure and the residue was partitioned between DCM and saturated NaHCO3. The organic layer was dried and concentrated to give 1-(4-(2-(4-((1H-benzo[d]imidazol-2-yl)(hydroxy)methyl)phenoxy)pyridin-3-yl)piperidin-1-yl)ethanone as off-white solid.

Workup

  1. filtrationThe catalyst was filtered off
  2. washwashed with THF
  3. additionTo the solution was added palladium on carbon, 10% (0.204 g, 0.192 mmol) and acetic acid, glacial (0.111 mL, 1.916 mmol)
  4. waitthe mixture was hydrogenated at 50 psi for another 24 h
  5. filtrationThe mixture was filtered through celite
  6. washwashed with THF
  7. customThe solvent was removed under reduced pressure
  8. customthe residue was partitioned between DCM and saturated NaHCO3
  9. customThe organic layer was dried
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-f05cb70a6675479bbe7dfbd51192a946
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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