Hydrochloric Acid → HCID 18386914, compound

HRID 651838Notes

Reaction equation

HRID 651838 reaction equation
[C:1](=[O:4])([O-])O.[Na+].Cl[C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].C(=O)([O-])[O-].[Na+].[Na+].C([N:25]([CH2:28][CH3:29])CC)C.[C:30](Cl)(=O)C(C)(C)C.[NH2:37][C:38]1[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=1.Cl.S(Cl)(C)(=O)=O.[OH-].[Na+]>O>[CH2:10]([O:9][C:7]([C:28]1([NH2:25])[CH2:29][CH2:30][N:37]([C:38]2[CH:45]=[CH:44][C:41]([C:42]#[N:43])=[CH:40][CH:39]=2)[C:1]1=[O:4])=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

11

Reactant 9

HCID 313Hydrochloric Acid2×HCID 8471Triethylamine2×HCID 10340Sodium CarbonateHCID 10387Benzyl chloroformateHCID 133964-AminobenzonitrileHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 62493Pivaloyl chlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 18386914HCID 18386914, compoundYield 49.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent3×

Conditions

Temperature
5 °C

Procedure

1883 g (9.52 mol) of 0-acetyl-L-homoserine hydrochloride are added to a solution of 1600 g (19.04 mol) of sodium hydrogen carbonate in 9.3 liters of water, and the mixture is cooled to 5° C. 1823 g (10.47 mol) of benzyl chloroformate are then added and the pH is maintained at 7.5 by addition of 20% sodium carbonate solution. The mixture is stirred for 2 hours at 15° C. and then extracted using 20 liters of methyl isobutyl ketone. The aqueous phase is adjusted to pH=2.0 using concentrated hydrochloric acid and extracted twice using a total of 25 liters of methyl isobutyl ketone. The combined organic phases are washed with 3.5 liters of water and concentrated in vacuo. The residue is taken up in 19.5 liters of methyl isobutyl ketone; 856 g (8.47 mol) of triethylamine are added and the mixture is cooled to 0C. 1042 g (8.47 mol) of pivaloyl chloride are then added and stirring is carried out for 20 minutes. After the addition of 1000 g (8.47 mol) of p-aminobenzonitrile, stirring is carried out for 36 hours at room temperature. 10 liters of water are then added and the pH is adjusted to 2.0 using concentrated hydrochloric acid. The organic phase is separated off; 10 liters of water are added and the pH is adjusted to 11 using 50% sodium hydroxide solution. After washing with 3 liters of water, the organic phase is concentrated in vacuo to about 3.5 kg. The residue is dissolved in 25 liters of methanol, and 7.5 liters of 25% ammonia are added. The mixture is then heated at 60° C. for 6 hours and then concentrated in vacuo. The residue is dehydrated by removal of 3×7.5 liters of methyl isobutyl ketone by distillation, is taken up in 25 liters of tetrahydrofuran and cooled to −5° C., and 1522 g (13.28 mol) of mesyl chloride are added. 1341 g (13.28 mol) of triethylamine are then added over a period of 45 minutes and stirring is carried out for one hour; then 2300 g of 50% sodium hydroxide solution are added and stirring is carried out for one hour. 3 liters of water are then added to the reaction mixture, and the pH is adjusted to 7 using concentrated hydrochloric acid. The solid obtained after removal of the tetrahydrofuran in vacuo is stirred with 14 liters of water, filtered off with suction and washed with water. The crude product is stirred with 19 liters of methyl isobutyl ketone at 50° C. and filtered off with suction. Drying yields 1401 g (44%) of 3-benzyloxycarbonyl-amino-1-(4-cyanophenyl)-2-oxo-pyrrolidine.

Workup

  1. extractionextracted
  2. extractionextracted twice
  3. washThe combined organic phases are washed with 3.5 liters of water
  4. concentrationconcentrated in vacuo
  5. stirringstirring
  6. waitis carried out for 20 minutes
  7. stirringstirring
  8. waitis carried out for 36 hours at room temperature
  9. customThe organic phase is separated off
  10. addition10 liters of water are added
  11. washAfter washing with 3 liters of water
  12. concentrationthe organic phase is concentrated in vacuo to about 3.5 kg
  13. dissolutionThe residue is dissolved in 25 liters of methanol
  14. addition7.5 liters of 25% ammonia are added
  15. temperatureThe mixture is then heated at 60° C. for 6 hours
  16. concentrationconcentrated in vacuo
  17. customThe residue is dehydrated by removal of 3×7.5 liters of methyl isobutyl ketone by distillation
  18. temperaturecooled to −5° C.
  19. stirringstirring
  20. waitis carried out for one hour
  21. stirringstirring
  22. waitis carried out for one hour
  23. customThe solid obtained
  24. customafter removal of the tetrahydrofuran in vacuo
  25. stirringis stirred with 14 liters of water
  26. filtrationfiltered off with suction
  27. washwashed with water
  28. stirringThe crude product is stirred with 19 liters of methyl isobutyl ketone at 50° C.
  29. filtrationfiltered off with suction
  30. customDrying

Sources & evidence

ORD record
ord-646cbf357ca24477bb0f4898815b3c23
Source dataset
uspto-grants-2001_08
Patent number
US06281364B1

Reaction notes

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