Water → HCID 58058025, compound

HRID 1908966Notes

Reaction equation

HRID 1908966 reaction equation
C(OC([NH:11][CH2:12][CH2:13][NH:14][C@H:15]([CH2:20][O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[C:16](OC)=[O:17])=O)C1C=CC=CC=1.C(OC(C)C)(C)C.O.C(Cl)Cl.C(O)(C)C>CO>[C:22]([O:21][CH2:20][C@H:15]1[NH:14][CH2:13][CH2:12][NH:11][C:16]1=[O:17])([CH3:25])([CH3:24])[CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 7914Diisopropyl EtherHCID 21966342Isopropanol methylene chlorideHCID 66660630HCID 66660630, compound

Product 1

HCID 58058025HCID 58058025, compoundYield 46.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

39.5 kg of (R)-methyl 2-(2-(benzyloxycarbonylamino)ethylamino)-3-t-butoxypropanoate was dissolved in 276 L of methanol in a reactor; purged with nitrogen; 5.9 kg of palladium/carbon (10% water mixture) was added and stirred for 3 hours while the hydrogen pressure was maintained at 10 bar. The reaction solution was filtered, concentrated under reduced pressure, and then again azeotroped by adding 30 L of isopropylether. 158 L (115 kg) of isopropylether, 39 L (35 kg) of ethyl acetate, and 36.4 kg of silica gel were added to a concentrated solution, stirred for 1 hour, decompression-filtered, and then concentrated under reduced pressure. A concentrated residue was azeotroped by adding 30 L of methanol, and then a concentrated solution and 221 L of methanol were added to a reactor. After purging with nitrogen, 11.85 kg of palladium/carbon (10% water mixture) was added, and then stirred for 6 hours while hydrogen pressure was maintained at 15 bar. The reaction solution was filtered, and then concentrated under reduced pressure. An aqueous layer was isolated in twice by adding 80 L of isopropylether and 80 L of purified water to the concentrated solution. An organic layer was isolated after adding methylene chloride/isopropanol=5:1 (126 L) to the aqueous layer and then stirring in 5 times. The organic layer was dehydration-filtered with 50 kg of sodium sulfate to obtain 9.7 kg of a title compound.

Workup

  1. custompurged with nitrogen
  2. addition5.9 kg of palladium/carbon (10% water mixture) was added
  3. temperaturewas maintained at 10 bar
  4. filtrationThe reaction solution was filtered
  5. concentrationconcentrated under reduced pressure
  6. customagain azeotroped
  7. additionby adding 30 L of isopropylether
  8. addition158 L (115 kg) of isopropylether, 39 L (35 kg) of ethyl acetate, and 36.4 kg of silica gel were added to a concentrated solution
  9. stirringstirred for 1 hour
  10. filtrationdecompression-filtered
  11. concentrationconcentrated under reduced pressure
  12. customA concentrated residue was azeotroped
  13. additionby adding 30 L of methanol
  14. additiona concentrated solution and 221 L of methanol were added to a reactor
  15. customAfter purging with nitrogen, 11.85 kg of palladium/carbon (10% water mixture)
  16. additionwas added
  17. stirringstirred for 6 hours while hydrogen pressure
  18. temperaturewas maintained at 15 bar
  19. filtrationThe reaction solution was filtered
  20. concentrationconcentrated under reduced pressure
  21. customAn aqueous layer was isolated in twice
  22. customAn organic layer was isolated
  23. stirringstirring in 5 times
  24. filtrationThe organic layer was dehydration-filtered with 50 kg of sodium sulfate

Sources & evidence

ORD record
ord-a85b1cd8ebf24981a73ce4edbdf23640
Source dataset
uspto-grants-2013_12
Patent number
US08598347B2

Reaction notes

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