Reaction #640560

ord-2b9bb2be7122499c90a9c461f4b21a10

Reaction equation

Cl
hydrochloric acid
O=C(O)C(=O)Cc1c[nH]c2ccccc12
Indole-3-pyruvic acid
CC(=O)C(=O)O
pyruvic acid
Cl.NO
hydroxylamine hydrochloride
O=C(O)C(=O)CC(O)(Cc1c[nH]c2ccccc12)C(=O)O
4-hydroxy-4-(3-indolylmethyl)-2-ketoglutaric acid
O=C(O)C(CC(O)(Cc1c[nH]c2ccccc12)C(=O)O)=NO
4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid
Yield 40.0%

Conditions

Temperature
35°CELSIUS
Detailed conditions
See reaction.notes.procedure_details.

Workup

  1. 1
    workup.WAITThe reaction was further continued for 4.5 hours
  2. 2
    Otherto yield a reaction mixture
  3. 3
    workup.ADDITIONwas added
  4. 4
    Extractionwere extracted with ethyl acetate
  5. 5
    WashAn organic layer was washed with saturated aqueous NaCl solution
  6. 6
    Concentrationconcentrated
  7. 7
    Otherto yield residue
  8. 8
    OtherThe residue was recrystallized from 60 mL of 28% aqueous ammonia and 350 mL of 2-propanol

Procedure

Indole-3-pyruvic acid (73.8 g, 352 mmol) was added to and dissolved in 917 g of an aqueous solution of 1.6 wt % sodium hydroxide. A temperature of the reaction mixture was maintained at 35° C. As the pH value was maintained at 11.1 using an aqueous solution of 30% sodium hydroxide, 310.2 g (1761 mmol) of an aqueous solution of 50% pyruvic acid was dripped over 2 hours. The reaction was further continued for 4.5 hours to yield a reaction mixture containing 4-hydroxy-4-(3-indolylmethyl)-2-ketoglutaric acid. As the pH value was maintained at 7 with the addition of the aqueous solution of 30% sodium hydroxide, 367.2 g (2114 mmol) of an aqueous solution of 40% hydroxylamine hydrochloride was added thereto, and stirred at 5° C. for 17.5 hours. The pH value of the reaction mixture was adjusted to 2 using concentrated hydrochloric acid, and organic matters were extracted with ethyl acetate. An organic layer was washed with saturated aqueous NaCl solution, and concentrated to yield residue. The residue was recrystallized from 60 mL of 28% aqueous ammonia and 350 mL of 2-propanol to yield 43.4 g of diammonium salt of 4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutaric acid (142 mmol, yield 40% versus indole-3-pyruvic acid) as crystal.

Source

DOI: 10.6084/m9.figshare.5104873.v1Patent: US08048647B2uspto-grants-2011_11