Water → 6-Bromo-3-isopropyl-[1,2,4]triazolo[4,3-a]pyridine

Temperature

7.5 °C

A 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer and a thermometer, was charged with 6-bromo-3-isopropyl-[1,2,4]triazolo(4,3-a)pyridine hydrochloride (587.0 g, 2.12 moles), water (1.2 L) and dichloromethane (1.8 L). The biphasic mixture was cooled to 5 to 10° C. using an ice-water bath. Sodium hydroxide (1N aqueous solution) (2.15 L) was added over a period of 10 minutes. The mixture was stirred in the bath for 15 minutes. The organic layer was then isolated and the aqueous layer extracted with dichloromethane (600 mL). The combined organic extracts are washed with 1:1 brine-water (2 L) and dried (MgSO4). Most of dichloromethane was removed by rotary evaporation. Ethyl acetate (800 ml) was then added. After removing about 400 ml of solvents, hexane (3.2 L) was added. The slurry was stirred in an ice-water bath for 2 hours and then filtered. The cake was washed with 9:1 hexane-ethyl acetate (3×150 ml) and dried in a vacuum-oven (30–35° C.) for 18 hours. The title compound (471.6 g, yield 92.5%), was obtained as a tan sandy powder.

1. customA 5 L three-necked round-bottomed flask, equipped with a mechanical stirrer
2. customThe organic layer was then isolated
3. extractionthe aqueous layer extracted with dichloromethane (600 mL)
4. washThe combined organic extracts are washed with 1:1 brine-water (2 L)
5. dry with materialdried (MgSO4)
6. customMost of dichloromethane was removed by rotary evaporation
7. additionEthyl acetate (800 ml) was then added
8. customAfter removing about 400 ml of solvents, hexane (3.2 L)
9. additionwas added
10. stirringThe slurry was stirred in an ice-water bath for 2 hours
11. filtrationfiltered
12. washThe cake was washed with 9:1 hexane-ethyl acetate (3×150 ml)
13. customdried in a vacuum-oven (30–35° C.) for 18 hours

ORD record

ord-7e5d601e8d54422b8076b0ff71f4510b

Source dataset

uspto-grants-2006_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07037923B2