反应 #157434

反应方程式

oxalyl chloride

tetrahydrofuran

magnesium

tetrahydrofuran

iodine

3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole

product

3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole

tetrahydrofuran

3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole

3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)-phenyl]-1H-pyrazole

→

oil

methyl 2-methyl-α-oxo-5-[1-[3-(trifluoromethyl)phenyl]-1H-pyrazol-3-yl]benzeneacetate

溶剂

methanol

ammonium chloride

water

反应条件

后处理

1. 1
   workup.ADDITIONthe addition
2. 2
   温度while heating
3. 3
   温度at reflux
4. 4
   温度Heating
5. 5
   workup.WAITwas continued for 2 h at −65° C.
6. 6
   温度to warm to room temperature
7. 7
   workup.STIRRINGstirred for 2 h
8. 8
   萃取extracted with ethyl acetate (2×)
9. 9
   洗涤The combined organic layers were washed with saturated aqueous sodium chloride
10. 10
    干燥dried over magnesium sulfate
11. 11
    过滤filtered
12. 12
    浓缩concentrated under reduced pressure
13. 13
    其他to give an oil
14. 14
    其他The oil was purified by medium pressure liquid chromatography (0 to 20% gradient of ethyl acetate in hexanes as eluant)

实验过程

To a mixture of magnesium turnings (0.17 g, 6.98 mmol) and 1,2-dibromoethane (2 drops) in tetrahydrofuran (0.5 mL) under a nitrogen atmosphere was added dropwise a solution of 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole (i.e. the product of Step C) (2.0 g, 5.25 mmol) in tetrahydrofuran (3.5 mL). After about 2% of the total volume of the 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)phenyl]-1H-pyrazole solution had been added, the addition was stopped and iodine (catalytic amount) was added to the reaction mixture. The remaining 3-(3-bromo-4-methylphenyl)-1-[3-(trifluoromethyl)-phenyl]-1H-pyrazole solution was then added to the reaction mixture over 1 h while heating at reflux. Heating was continued for an additional 45 minutes, and then the reaction mixture was cooled to room temperature. The reaction mixture was added via an addition funnel to a solution of oxalyl chloride (0.508 mL, 5.82 mmol) in tetrahydrofuran (6 mL) at −65° C. Stirring was continued for 2 h at −65° C., and then methanol (1.17 mL) was added to the reaction mixture, and the mixture was allowed to warm to room temperature and stirred for 2 h. The reaction mixture was diluted with saturated aqueous ammonium chloride (4 mL) and water (8 mL) and then extracted with ethyl acetate (2×). The combined organic layers were washed with saturated aqueous sodium chloride, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give an oil. The oil was purified by medium pressure liquid chromatography (0 to 20% gradient of ethyl acetate in hexanes as eluant) to provide an oil (0.31 g). The oil was crystallized from hexanes-diethyl ether to provide the title compound, a compound of the present invention, as a solid (200 mg).

来源