Phosgene → HCID 11207924, compound

HRID 1059088Notes

Reaction equation

HRID 1059088 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH:5]1([C@@H:11]([NH:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[C:12]([OH:14])=[O:13])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1>O1CCCC1>[CH:5]1([C@@H:11]2[C:12](=[O:14])[O:13][C:1](=[O:2])[N:15]2[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1

Participants

4

Reactant 2

HCID 6371PhosgeneHCID 11447897HCID 11447897, compound

Product 1

HCID 11207924HCID 11207924, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phosgene (28.9 kg, 291.9 mol) was added to (2R)-2-cyclohexyl-2-[(2-ethoxy-2-oxoethyl) amino]ethanoic acid (44.2 kg, 182 mol, obtained analogously to the method described in step (c) (Alternative A) above) in tetrahydrofuran (340 kg) at 40° C. over one hour. The reaction was deemed to be complete after a further hour. The mixture was concentrated at reduced pressure. The residue was diluted with tetrahydrofuran (272.6 kg) and the pH was adjusted at 0° C. to 6.5 with N-methylmorpholine (15.3 kg). The reaction was continued for a further 45 minutes. HCI/dioxane (0.34 kg) was then added and the residue was filtered through Celite®. The filter cake was washed twice with tetrahydrofuran. The combined filtrates were concentrated at reduced pressure at 20° C. To the residue was added heptane (250 kg), and the mixture was concentrated again. To the resultant residue further heptane (81 kg) was added. The temperature was adjusted to 0° C. and the mixture was allowed to crystallise for five hours. The crystals were filtered, washed (3×30 kg heptane) and dried (low pressure, 20° C.), to yield 46 kg (95%) of the sub-title compound.

Workup

  1. customobtained analogously to the method
  2. customat 40° C.
  3. customover one hour
  4. waitto be complete after a further hour
  5. concentrationThe mixture was concentrated at reduced pressure
  6. additionThe residue was diluted with tetrahydrofuran (272.6 kg)
  7. customwas adjusted at 0° C. to 6.5 with N-methylmorpholine (15.3 kg)
  8. additionHCI/dioxane (0.34 kg) was then added
  9. filtrationthe residue was filtered through Celite®
  10. washThe filter cake was washed twice with tetrahydrofuran
  11. concentrationThe combined filtrates were concentrated at reduced pressure at 20° C
  12. additionTo the residue was added heptane (250 kg)
  13. concentrationthe mixture was concentrated again
  14. additionTo the resultant residue further heptane (81 kg) was added
  15. customwas adjusted to 0° C.
  16. customto crystallise for five hours
  17. filtrationThe crystals were filtered
  18. washwashed (3×30 kg heptane)
  19. customdried (low pressure, 20° C.)

Sources & evidence

ORD record
ord-4362ee7108a94b1db7699931f20c8cf0
Source dataset
uspto-grants-2003_02
Patent number
US06518434B2

Reaction notes

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