HCID 71086630, compound → HCID 71086819, compound

HRID 538653Notes

Reaction equation

HRID 538653 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[CH2:5][NH:6][C:7]([C:9]1[C:14]([O:15]CC2C=CC=CC=2)=[CH:13][C:12]([O:23]CC2C=CC=CC=2)=[CH:11][N:10]=1)=[O:8])[CH3:2]>[Pd].C(O)C>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][NH:6][C:7]([C:9]1[C:14]([OH:15])=[CH:13][C:12]([OH:23])=[CH:11][N:10]=1)=[O:8])[CH3:2]

Participants

4

Reactant 1

HCID 71086630HCID 71086630, compound

Product 1

HCID 71086819HCID 71086819, compoundYield 97.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Conditions

Temperature
13 °C

Procedure

To a 20 L round-bottomed flask was charged nitrogen and palladium on carbon (10% Pd/C) (100 g, 60% wet paste) and ethanol (12 L), followed by the addition of [(3,5-bis-benzyloxypyridine-2-carbonyl)-amino]-acetic acid ethyl ester, 1, (1000 g, 2.378 mol). The resulting mixture was subjected to a vacuum-nitrogen purge cycle three times and a vacuum-hydrogen purge cycle three times. A hydrogen atmosphere was introduced and the reaction mixture was stirred at 1-25° C. until the completion of the reaction by TLC analysis. The reaction typically lasted 2 to 3 hours and a vigorous stirring was important to complete the reaction. The reaction system was then subjected to a vacuum-nitrogen purge cycle to remove hydrogen from the system. The reaction mixture was filtered and the filter-cake was washed with ethanol (2 L). The combined filtrate was concentrated on a rotary evaporator at up to 45° C. bath temperature to a constant weight to provide 558 g (97.7% yield) of the desired product as an off-white solid. MP: 138-140° C.; MS (ESI+): m/z 241 (M+1); 1H NMR (300 MHz, DMSO-d6) δ 12.28 (s, 1H), 10.79 (s, 1H), 9.09-9.05 (t, J=6 Hz, 1H), 7.76-7.71 (d, J=2.4 Hz, 1H), 6.68-6.67 (d, J=2.1 Hz, 1H), 4.15-4.08 (q, J=6.9 Hz, 2H), 4.02-4.00 (d, J=6.3 Hz, 2H), 1.22-1.17 (t, J=6.9 Hz, 2H).

Workup

  1. custompurge cycle three times
  2. customa vacuum-hydrogen purge cycle three times
  3. additionA hydrogen atmosphere was introduced
  4. customThe reaction typically lasted 2 to 3 hours
  5. stirringa vigorous stirring
  6. customthe reaction
  7. custompurge cycle
  8. customto remove hydrogen from the system
  9. filtrationThe reaction mixture was filtered
  10. washthe filter-cake was washed with ethanol (2 L)
  11. concentrationThe combined filtrate was concentrated on a rotary evaporator at up to 45° C. bath temperature to a constant weight

Sources & evidence

ORD record
ord-cd7099bfe81649499be8b55b5152b0fa
Source dataset
uspto-grants-2014_10
Patent number
US08865748B2

Reaction notes

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