L-Glutamine → N-Phthaloyl-L-glutamine

HRID 1020156Notes

Reaction equation

HRID 1020156 reaction equation
[NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[NH2:6].C(=O)([O-])[O-].[Na+].[Na+].C(N1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32])(OCC)=O>O>[CH:29]1[CH:28]=[C:25]2[C:26]([N:1]([C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5]([NH2:6])=[O:7])[C:23](=[O:32])[C:24]2=[CH:31][CH:30]=1)=[O:27]

Participants

5

Reactant 3

HCID 5961L-GlutamineHCID 10340Sodium CarbonateHCID 31187N-Carbethoxyphthalimide

Product 1

HCID 259136N-Phthaloyl-L-glutamine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of deuterium enriched glutamine and sodium carbonate in water is rapidly added N-carbethoxyphthalimide as a solid. After 1 hour, the reaction mixture is filtered to remove unreacted N-carbethoxyphthalimide. The pH of the stirred filtrate is adjusted to 3-4 with 4N HCl. The mixture is then seeded with N-phthaloyl-L-glutamine and the pH adjusted to 1-2 with 4N HCl. The resulting slurry is stirred for 1 hour. The slurry is filtered and the solid washed with water. The solid is dried to afford N-phthaloyl-L-glutamine. N-phthaloyl glutamine, carbonyldiimidazole, and 4-dimethylaminopyridine in anhydrous THF is heated to reflux for 16 hours. The reaction slurry is filtered and the solid washed with methylene chloride. The solid is dried to provide deuterium-enriched thalidomide. Carbon-13 enrichment and nitrogen-15 enrichment of thalidomide may be achieved using similar methods by utilizing the appropriate carbon-13 or nitrogen-15 labeled glutamine starting material.

Workup

  1. filtrationthe reaction mixture is filtered
  2. customto remove unreacted N-carbethoxyphthalimide
  3. filtrationThe slurry is filtered
  4. washthe solid washed with water
  5. customThe solid is dried

Sources & evidence

ORD record
ord-ae8df4c76d0548a18fefdede94251e2f
Source dataset
uspto-grants-2014_05
Patent number
US08716314B2

Reaction notes

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