Hydrochloric Acid → 4-Hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutarate ammonium salt

Temperature

5 °C

73.8 g (352 mmol) of indol-3-pyruvic acid was added to and dissolved in 917 g of 1.6 wt % aqueous sodium hydroxide. The temperature of the reaction solution was adjusted to 35° C. While the pH of the solution was kept at 11.1 with 30% aqueous sodium hydroxide, 310.2 g (1761 mmol) of 50% aqueous pyruvic acid was added dropwise over 2 hours. The reaction mixture was further reacted for 4.5 hours to obtain a reaction solution containing 4-hydroxy-4-(3-indolylmethyl)-2-ketoglutaric acid. While the pH of this reaction solution was kept at 7 with 30% aqueous sodium hydroxide, 367.2 g (2114 mmol) of 40% aqueous hydroxylamine hydrochloride was added thereto, and the mixture was stirred at 5° C. for 17.5 hours. The pH value of the reaction solution was adjusted to 2 with concentrated hydrochloric acid, and its organic matter was then extracted with ethyl acetate. The organic layer was washed with saturated saline and then concentrated to obtain residues. The residues were subjected to recrystallization from 60 ml of 28% ammonia water and 1350 ml of 2-propanol to obtain 43.4 g of 4-hydroxy-4-(3-indolylmethyl)-2-hydroxyiminoglutarate diammonium salt (142 mmol: yield 40% relative to indol-3-pyruvic acid) as crystals.

1. customwas adjusted to 35° C
2. additionwas added dropwise over 2 hours
3. customThe reaction mixture was further reacted for 4.5 hours
4. customto obtain a reaction solution
5. additionwas added
6. extractionwas then extracted with ethyl acetate
7. washThe organic layer was washed with saturated saline
8. concentrationconcentrated
9. customto obtain residues
10. customThe residues were subjected to recrystallization from 60 ml of 28% ammonia water and 1350 ml of 2-propanol

ORD record

ord-02f55ea4b9014151b06c6b99a89e175b

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08043836B2