Diethyl Ether → 3,5-dibromo-1H-pyrazole-4-carbaldehyde

Temperature

-75 °C

81.7 g (0.268 mol) of 3,4,5-tribromopyrazole are introduced with stirring into 1500 cm3 of diethyl ether at a temperature in the region of 20° C. and under an argon atmosphere. The mixture is cooled to a temperature in the region of −78° C. and 335 cm3 (0.536 mol) of n-butyllithium at 1.6 mol/l are then added dropwise over 3 hours 15 minutes. The reaction mixture is stirred for 1.5 hours at a temperature in the region of −75° C., followed by dropwise addition of 100 cm3 (1.34 mol) of dimethylformamide, while keeping the temperature below −70° C. Stirring is continued for 2 hours at a temperature in the region of −75° C., and then for 15 hours at a temperature in the region of 20° C. The reaction medium is then cooled in an ice bath and 1000 cm3 of water are added. After separation of the phases by settling, the aqueous phase is extracted with 500 cm3 of diethyl ether and with 3 times 500 cm3 of ethyl acetate. The aqueous phase is then acidified with citric acid solution to pH 3 (the formation of a precipitate is observed) and extracted with twice 1000 cm3 of diethyl ether. The organic phase is dried over magnesium sulfate and concentrated to dryness under reduced pressure (2.7 kPa), and the yellow solid obtained is taken up in 300 cm3 of water and stirred for 2 hours at a temperature in the region of 20° C. The mixture is then filtered and the solid is washed with twice 50 cm3 of water, dried under a ventilated hood and then dried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C. 51.3 g of 3,5-dibromo-1H-pyrazole-4-carboxaldehyde are thus obtained in the form of a yellow powder melting at 173° C.

1. additionare then added dropwise over 3 hours 15 minutes
2. customthe temperature below −70° C
3. stirringStirring
4. waitis continued for 2 hours at a temperature in the region of −75° C.
5. waitfor 15 hours at a temperature in the region of 20° C
6. temperatureThe reaction medium is then cooled in an ice bath
7. customAfter separation of the phases
8. extractionthe aqueous phase is extracted with 500 cm3 of diethyl ether and with 3 times 500 cm3 of ethyl acetate
9. extractionextracted with twice 1000 cm3 of diethyl ether
10. dry with materialThe organic phase is dried over magnesium sulfate
11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
12. customthe yellow solid obtained
13. stirringstirred for 2 hours at a temperature in the region of 20° C
14. filtrationThe mixture is then filtered
15. washthe solid is washed with twice 50 cm3 of water
16. customdried under a ventilated hood
17. customdried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C

ORD record

ord-b27dbc178d2949d08eb94068409ab76b

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07884123B2