Hydrochloric Acid → HCID 67166079, compound

HRID 552076Notes

Reaction equation

HRID 552076 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]1[NH2:8].C(OCC)(=O)C.[CH2:15]([O:22][C:23]([N:25]1[CH2:29][C:28](O)=[CH:27][C:26]1=[O:31])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[ClH:32]>C(O)C>[ClH:32].[CH2:15]([O:22][C:23]([N:25]1[CH2:29][C:28]([NH:1][C@@H:2]2[CH2:7][CH2:6][CH2:5][CH2:4][C@H:3]2[NH2:8])=[CH:27][C:26]1=[O:31])=[O:24])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl Acetate3×HCID 438061,2-Diaminocyclohexane, trans-2×HCID 54687511HCID 54687511, compound

Product 1

HCID 67166079HCID 67166079, compoundYield 90.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent3×

Conditions

Temperature
60 °C

Procedure

(1R,2R)-1,2-diaminocyclohexane 2294 g (20.09 mol) was dissolved in 3.1 L of ethanol to make a solution. To a 100 L glass lined reactor equipped with a stirrer, were added 26.8 L of ethyl acetate, 4635 g of 4-hydroxy-2-oxo-3-pyrroline-1-carboxylic acid benzyl ester (content: 96.2%, 19.12 mol) synthesized according to the methods of Non-Patent Reference 9 and 12.5 L of ethanol, furthermore, a previously prepared ethanol solution of (1R,2R)-1,2-diaminocyclohexane was added at 15 to 21° C. For washing, 2.2 L of ethanol was used. Next, 3.35 L of 6M hydrochloric acid (20.1 mol) was added at 19 to 25° C. For washing, 0.3 L of water was used. The reaction mixture was heated to 60° C., and reacted at the same temperature for 3 hours. While holding the temperature at approximately 60° C., 4.4 L of ethyl acetate was added, the mixture was cooled to 50° C., 2.4 g of seed crystal was added, and the solution was kept at 50° C. for one hour. While holding the temperature at approximately 50° C., 22.3 L of ethyl acetate was added over one hour, the solution was kept at 50° C. for one hour, cooling to 10° C. over 4.6 hours, and kept at 10° C. for another 10 hours. The deposited solid was separated with a centrifuge, and washed with 17.8 L of a cooled mixed solution of ethyl acetate-ethanol (volume ratio: 75:25). The obtained wet solid was dried under reduced pressure at 50° C. for 19 hours to obtain 6342 g of 4-[(1R,2R)-2-aminocyclohexylamino]-2-oxo-3-pyrroline-1-carboxylic acid benzyl ester hydrochloride.

Workup

  1. customequipped with a stirrer
  2. customsynthesized
  3. washFor washing
  4. washFor washing
  5. customreacted at the same temperature for 3 hours
  6. customat approximately 60° C.
  7. temperaturethe mixture was cooled to 50° C.
  8. addition2.4 g of seed crystal was added
  9. customat approximately 50° C.
  10. waitthe solution was kept at 50° C. for one hour
  11. temperaturecooling to 10° C. over 4.6 hours
  12. waitkept at 10° C. for another 10 hours
  13. customThe deposited solid was separated with a centrifuge
  14. washwashed with 17.8 L of a cooled
  15. additionmixed solution of ethyl acetate-ethanol (volume ratio: 75:25)
  16. customThe obtained wet solid was dried under reduced pressure at 50° C. for 19 hours

Sources & evidence

ORD record
ord-e20852a376724023bc97d916288dea9a
Source dataset
uspto-grants-2011_05
Patent number
US07951799B2

Reaction notes

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