반응 #2363202

반응 방정식

4-bromo-5-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazole

product

4-bromo-5-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazole

2,4-difluorobenzaldehyde

n-butyllithium

→

title compound

α-(2,4-difluorophenyl)-5-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazole-4-methanol

용매

tetrahydrofuran

ammonium chloride

tetrahydrofuran

반응 조건

후처리

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

실험 절차

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 (1534, 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).

출처