2,4-Difluorobenzaldehyde → HCID 66613811, compound

Temperature

-78 °C

To a mixture of 4-bromo-5-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazole (i.e. the product of Step C) (500 mg, 1.7 mmol) in tetrahydrofuran (15 mL) at −78° C. was added dropwise n-butyllithium (2.0 M in hexanes, 0.76 mL, 1.9 mmol). The reaction mixture was stirred at −78° C. for about 20 minutes, and then a solution of 2,4-difluorobenzaldehyde (153 μL, 1.4 mmol) in tetrahydrofuran (1 mL) was added dropwise. After the addition was complete, the reaction mixture was stirred at about −78° C. for about 15 minutes, and then diluted with saturated aqueous ammonium chloride solution (1 mL) and allowed to warm to room temperature. The resulting mixture was poured onto a solid phase extraction tube (Varian Chem Elute®, prepacked with diatomaceous earth) eluting with ethyl acetate (50 mL). The ethyl acetate eluant was concentrated under reduced pressure and the resulting material was purified by MPLC (20 to 50% gradient of ethyl acetate in hexanes as eluant) to provide the title compound, a compound of the present invention, as a solid (560 mg).

1. additionAfter the addition
2. stirringthe reaction mixture was stirred at about −78° C. for about 15 minutes
3. temperatureto warm to room temperature
4. additionThe resulting mixture was poured onto a solid phase extraction tube (Varian Chem Elute®, prepacked with diatomaceous earth)
5. washeluting with ethyl acetate (50 mL)
6. concentrationThe ethyl acetate eluant was concentrated under reduced pressure
7. customthe resulting material was purified by MPLC (20 to 50% gradient of ethyl acetate in hexanes as eluant)

ORD record

ord-d30cb817e1344e638411210a1f561ded

Source dataset

uspto-grants-2014_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08754115B2