Hydrochloric Acid → HCID 12310809, compound

Indole (5.86 g) was dissolved in dichloromethane (50 ml) and to the solution was added dropwise 2.89 M solution of methyl magnesium bromide in diethyl ether (40 ml) over a period of 45 minutes at room temperature. After the dropwise addition was completed, the mixture was stirred for 45 minutes at room temperature. Under cooling at −10° C., a solution of ethyl (2RS,3SR)-2,3-epoxybutanoate (6.51 g) in dichloromethane (50 ml) was added dropwise over a period of 20 minutes. The mixture was stirred for 1 hour at −10 ° C. To the mixture was added 1 N aqueous solution of hydrochloric acid (150 ml). The organic layer was removed, and the aqueous layer was extracted with dichloromethane (50 ml). The organic layers were combined, and concentrated under reduced pressure. The residue was dissolved by adding ethanol (56 ml) and water (24 ml). To the solution was added 1 N aqueous solution of sodium hydroxide (50 ml) under ice cooling. The mixture was stirred for 3.5 hours under ice cooling and 12 hours at room temperature. To the mixture was added 1 N aqueous solution of sodium hydroxide (25 ml), and the mixture was stirred for 1 hour at room temperature. The ethanol was distilled off under reduced pressure, and aqueous layer was washed twice with ethyl acetate (70 ml). The aqueous layer was acidified by adding conc. hydrochloric acid (10 ml). The mixture was extracted twice with ethyl acetate (100 ml). The ethyl acetate layers were combined and dried over anhydrous magnesium sulfate. To the ethyl acetate layer was added activated carbon (1 g) and mixture was stirred. After filtration, the filtrate was concentrated under reduced pressure. The residue was recrystallized from water to give (2RS,3SR)-2-hydroxy-3-(indol-3-yl)butyric acid (7.27 g) as pale brown solid.

1. additionAfter the dropwise addition
2. temperatureUnder cooling at −10° C.
3. stirringThe mixture was stirred for 1 hour at −10 ° C
4. customThe organic layer was removed
5. extractionthe aqueous layer was extracted with dichloromethane (50 ml)
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved
8. additionby adding ethanol (56 ml) and water (24 ml)
9. additionTo the solution was added 1 N aqueous solution of sodium hydroxide (50 ml) under ice cooling
10. stirringThe mixture was stirred for 3.5 hours under ice cooling and 12 hours at room temperature
11. additionTo the mixture was added 1 N aqueous solution of sodium hydroxide (25 ml)
12. stirringthe mixture was stirred for 1 hour at room temperature
13. distillationThe ethanol was distilled off under reduced pressure, and aqueous layer
14. washwas washed twice with ethyl acetate (70 ml)
15. additionby adding conc. hydrochloric acid (10 ml)
16. extractionThe mixture was extracted twice with ethyl acetate (100 ml)
17. dry with materialdried over anhydrous magnesium sulfate
18. additionTo the ethyl acetate layer was added activated carbon (1 g) and mixture
19. stirringwas stirred
20. filtrationAfter filtration
21. concentrationthe filtrate was concentrated under reduced pressure
22. customThe residue was recrystallized from water

ORD record

ord-b89213d7c05148bcb2aea27262602328

Source dataset

uspto-grants-2001_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06265586B1