3-Benzyloxy-1-[(phenylbenzylcarbamoyl)methyl]-2-(1H)-pyridinone → 3-Hydroxy-1-[(phenylbenzylcarbamoyl)methyl]-2-(1H)-pyridinone

HRID 1678377Notes

Reaction equation

HRID 1678377 reaction equation
C([O:8][C:9]1[C:10](=[O:32])[N:11]([CH2:15][C:16](=[O:31])[N:17]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][CH:14]=1)C1C=CC=CC=1.[H][H]>CCO.[Pd].[Fe+3]>[OH:8][C:9]1[C:10](=[O:32])[N:11]([CH2:15][C:16](=[O:31])[N:17]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 2

HCID 667463123-Benzyloxy-1-[(phenylbenzylcarbamoyl)methyl]-2-(1H)-pyridinoneHCID 178418361HCID 178418361, compound

Product 1

HCID 673739623-Hydroxy-1-[(phenylbenzylcarbamoyl)methyl]-2-(1H)-pyridinoneYield 22%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 29936Ferric cationCatalystHCID 702EthanolSolvent2×

Procedure

18 (280 mg, 0.7 mmol) was suspended in 150 mL of EtOH. 10% (w/w, 38 mg) of 10% Pd/C catalyst was added to the hydrogenation flask (500 mL Pyrex® Parr reaction bottle tested to 120 psi, max. working pressure of 60 psi). The Parr hydrogenation system located in the VanNieuwenhze lab was used for the deprotection reactions. The hydrogen pressure was set to 35 psi with agitation, and the process went on for 19 h. A white precipitate was present even after the reaction was stopped, but this white product reacted with iron(III) to give a pink product instead of no reaction as with the protected starting material. The catalyst was removed by vacuum filtration and separated from the product by dissolving the white precipitate in 100 mL hot CH2Cl2. An additional batch of product was isolated by cooling the EtOH filtrate to 0° C. for 2 h. The clear solution was concentrated by rotary evaporation to yield a white solid. The solid was washed with MeOH to remove residual DCU. Yield: 22%. 1H NMR (d6-DMSO, 400 MHz, 25° C.): δ 4.34 (d, J=6.0 Hz, 2H, —CH2—), 4.63 (s, 2H, —CH2—), 6.08 (t, J=7.2 Hz, 1H, Ar—H), 6.69 (d, J=7.2 Hz, 1H, Ar—H), 7.10 (d, J=6.4 Hz, 1H, Ar—H), 7.44 (m, 5H, Bz-H), 7.64 (m, 4H, Phenyl-H), 8.70 (t, J=5.6 Hz, 1H, —NH—), 9.02 (s, 1H, —OH). APCI-MS: m/z 334.9 [M+H]+. Anal. Calcd for C20H18N2O3: C, 71.84; H, 5.43; N, 8.38. Found: C, 71.49; H, 5.78; N, 8.52.

Workup

  1. customwent on for 19 h
  2. customto give a pink product
  3. custominstead of no reaction as with the
  4. customThe catalyst was removed by vacuum filtration
  5. customseparated from the product
  6. dissolutionby dissolving the white precipitate in 100 mL hot CH2Cl2
  7. customAn additional batch of product was isolated
  8. concentrationThe clear solution was concentrated by rotary evaporation
  9. customto yield a white solid
  10. washThe solid was washed with MeOH
  11. customto remove residual DCU

Sources & evidence

ORD record
ord-a2579d952ca64db7bea33294d065d39d
Source dataset
uspto-grants-2011_08
Patent number
US08008510B2

Reaction notes

Loading…