2-(溴甲基)-5-乙氧基-1,3-二氟苯

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 46.9 g of ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate 1-15-1 (266 mmol, 1.0 eq.) in 588 mL THF were cooled to 0° C. and 11.6 g sodiumhydride (60%, 290 mmol, 1.2 eq.) were added in small portions. The resulting suspension was diluted with 250 mL THF. 66.7 g 2-(bromomethyl)-5-ethoxy-1,3-difluorobenzene (266 mmol, 1.1 eq., commercially available) were added slowly. The reaction mixture was stirred at rt for 2 hours. 300 mL water was added and the THF was evaporated in vacuum. The aqueous residue was extracted with ethylacetate three times. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to provide 79.8 g (195 mmol, 81%) of 89% pure target compound. the THF was evaporated in vacuum The aqueous residue was extracted with ethylacetate three times The combined organic layers were dried over a silicone filter concentrated in vacuo The residue was purified by flash chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 46.9 g of ethyl 5-cyclopropyl-4-methyl-1H-pyrazole-3-carboxylate 1-15-1 (266 mmol, 1.0 eq.) in 588 mL THF were cooled to 0° C. and 11.6 g sodiumhydride (60%, 290 mmol, 1.2 eq.) were added in small portions. The resulting suspension was diluted with 250 mL THF. 66.7 g 2-(bromomethyl)-5-ethoxy-1,3-difluorobenzene (266 mmol, 1.1 eq., commercially available) were added slowly. The reaction mixture was stirred at rt for 2 hours. 300 mL water was added and the THF was evaporated in vacuum. The aqueous residue was extracted with ethylacetate three times. The combined organic layers were dried over a silicone filter and concentrated in vacuo. The residue was purified by flash chromatography to provide 79.8 g (195 mmol, 81%) of 89% pure target compound. the THF was evaporated in vacuum The aqueous residue was extracted with ethylacetate three times The combined organic layers were dried over a silicone filter concentrated in vacuo The residue was purified by flash chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: 3.40 g of 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carbonitrile (CAS-RN 851776-29-9) (25.5 mmol, 1.00 eq) were dissolved in 35 mL dry DMF under nitrogen atmosphere. 7.05 g 2-(bromomethyl)-5-ethoxy-1,3-difluorobenzene (28.1 mmol, 1.10 eq.) and 9.98 g cesiumcarbonate (30.1 mmol, 1.20 eq.) were added and stirred over night at rt. DCM and water were added, the aqueous phase was washed twice with DCM, the organic phase was washed with brine and was dried with magnesiumsulfate, was concentrated in vacuo and purified by flash chromatography (hexane/tert-butyl methyl ether-gradient with hexane 100-70%) to provide 1.07 g (3.45 mmol, 14%) of the analytically pure target compound. the aqueous phase was washed twice with DCM the organic phase was washed with brine was dried with magnesiumsulfate was concentrated in vacuo purified by flash chromatography (hexane/tert-butyl methyl ether-gradient with hexane 100-70%) to provide 1.07 g (3.45 mmol, 14%) of the analytically pure target compound