Water → HCID 58294639, compound

HRID 2272018Notes

Reaction equation

HRID 2272018 reaction equation
S(=O)(=O)(O)O.O.[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[C:13](=O)[C:14]3[C:19]([C:20]=2[CH:21]=1)=[CH:18][CH:17]=[CH:16][N:15]=3>[Pd].CO>[CH3:7][O:8][C:9]1[CH:10]=[CH:11][C:12]2[CH2:13][C@H:14]3[C@@H:19]([C:20]=2[CH:21]=1)[CH2:18][CH2:17][CH2:16][NH:15]3

Participants

6

Reactant 3

HCID 962WaterHCID 1118Sulfuric AcidHCID 58294438HCID 58294438, compound

Product 1

HCID 58294639HCID 58294639, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of sulfuric acid (98%, 6 kg), water (6 L), and methanol (6 L) is added to an autoclave charged with 6-methoxy-indeno[2,1-b]pyridin-9-one (1.2 kg) and wet 10% palladium on carbon (50%, 0.48 kg). The autoclave is purged with nitrogen and filled then with hydrogen (100 psi). The mixture is heated to 60° C. and maintained at this temperature and hydrogen pressure until the starting material is completely consumed (2-12 h). The mixture is cooled to 50-55° C. and filtered over Celite. The Celite is washed with a warm 1:1 mixture of water and methanol several times (total 20 L). The combined filtrate is added to an autoclave charged with wet 10% palladium on carbon (50%, 0.96 kg). The autoclave is purged with nitrogen and filled then with hydrogen (100 psi). The mixture is heated to 60° C. and maintained at this temperature and hydrogen pressure until the intermediate is completely consumed (12-24 h). The mixture is cooled to ambient temperature and filtered over Celite. The Celite is washed with a mixture of methanol and water (5 L/5 L). The combined filtrate is cooled to 0-10° C. and the pH value is adjusted to 10-11 using 30% aqueous NaOH solution while maintaining the solution temperature below 40° C. Water (10 L) is added and the resulting mixture is extracted with dichloromethane (2×5 L). The combined extract is washed with 10% aqueous NaCl solution and concentrated. The residue is taken up twice in methyl ethyl ketone and concentrated again to give the crude title compound.

Workup

  1. additionis added to an autoclave
  2. customThe autoclave is purged with nitrogen
  3. additionfilled
  4. temperaturemaintained at this temperature and hydrogen pressure until the starting material
  5. customis completely consumed (2-12 h)
  6. temperatureThe mixture is cooled to 50-55° C.
  7. filtrationfiltered over Celite
  8. washThe Celite is washed with
  9. temperaturea warm
  10. addition1:1 mixture of water and methanol several times (total 20 L)
  11. additionThe combined filtrate is added to an autoclave
  12. additioncharged with wet 10% palladium on carbon (50%, 0.96 kg)
  13. customThe autoclave is purged with nitrogen
  14. additionfilled
  15. temperatureThe mixture is heated to 60° C.
  16. temperaturemaintained at this temperature and hydrogen pressure until the intermediate
  17. customis completely consumed (12-24 h)
  18. temperatureThe mixture is cooled to ambient temperature
  19. filtrationfiltered over Celite
  20. washThe Celite is washed with a mixture of methanol and water (5 L/5 L)
  21. temperatureThe combined filtrate is cooled to 0-10° C.
  22. temperaturewhile maintaining the solution temperature below 40° C
  23. additionWater (10 L) is added
  24. extractionthe resulting mixture is extracted with dichloromethane (2×5 L)
  25. extractionThe combined extract
  26. washis washed with 10% aqueous NaCl solution
  27. concentrationconcentrated
  28. concentrationconcentrated again

Sources & evidence

ORD record
ord-403eaddcdcdc461e84d1186faebfebac
Source dataset
uspto-grants-2015_09
Patent number
US09120769B2

Reaction notes

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