Hydrochloric Acid → 3-(L-gamma-glutamylamino)benzoic acid

HRID 2402927Notes

Reaction equation

HRID 2402927 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:8]([O:10]C(C)(C)C)=[O:9])[CH2:3][CH2:4][C:5](=O)[OH:6].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:46][C:47]1[CH:48]=[C:49]([CH:55]=[CH:56][CH:57]=1)[C:50]([O:52]CC)=[O:51].O.[OH-].[Li+].[OH-].[Li+].Cl>CN(C=O)C.O.C(O)C.C(N(CC)CC)C>[NH2:1][C@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5]([NH:46][C:47]1[CH:48]=[C:49]([CH:55]=[CH:56][CH:57]=1)[C:50]([OH:52])=[O:51])=[O:6]

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11400Ethyl 3-aminobenzoateHCID 168937Lithium hydroxide, monohydrateHCID 6993444(4S)-5-(tert-butoxy)-4-{[(tert-butoxy)carbonyl]amino}-5-oxopentanoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 98382053-(L-gamma-glutamylamino)benzoic acidYield 61%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

Boc-Glu-OtBu (100 mg, 0.33 mmol) and HATU (150.4 mg, 0.40 mmol) were dissolved in 2 mL of DMF. Triethylamine (68.5 μL) was added thereto and stirred for 10 minutes. Ethyl 3-aminobenzoate (49.2 mg, 0.33 mmol) was added thereto and stirred overnight. After liquid separation was conducted with an ethyl acetate and an aqueous solution of 1M sodium hydroxide, the organic layer was washed with an aqueous solution of 1M sodium hydroxide, 1M hydrochloric acid and a saturated saline solution, successively, and dried with sodium sulfate to remove a solvent. The obtained residue was dissolved in 2 mL of THF, 1 mL of ethanol and 1 mL of water, and lithium hydroxide monohydrate (13.5 mg, 0.32 mmol) was added thereto. After stirring the mixture for 5 hours, 4.5 mg of lithium hydroxide was added thereto and stirred overnight. After confirming the completion of the reaction, pH of the reaction solution was adjusted to 2 with 1M hydrochloric acid, and a solvent was removed therefrom. 3 mL of TFA was added to the obtained residue and stirred at room temperature for 5 hours. After removing a solvent, purification was conducted in accordance with the purification process A to obtain a title compound.

Workup

  1. stirringstirred overnight
  2. customAfter liquid separation
  3. washan aqueous solution of 1M sodium hydroxide, the organic layer was washed with an aqueous solution of 1M sodium hydroxide, 1M hydrochloric acid
  4. dry with materiala saturated saline solution, successively, and dried with sodium sulfate
  5. customto remove a solvent
  6. dissolutionThe obtained residue was dissolved in 2 mL of THF
  7. stirringAfter stirring the mixture for 5 hours
  8. stirringstirred overnight
  9. customthe completion of the reaction, pH of the reaction solution
  10. customa solvent was removed
  11. addition3 mL of TFA was added to the obtained residue
  12. stirringstirred at room temperature for 5 hours
  13. customAfter removing
  14. customa solvent, purification

Sources & evidence

ORD record
ord-ecfc9eecc07547eca7d0164db25a8768
Source dataset
uspto-grants-2014_08
Patent number
US08796485B2

Reaction notes

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