1,2-二氟-3-甲苯

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

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

实验步骤: Under a nitrogen atmosphere, 30 g the compound (2) having been dissolved in 240 mL of THF was cooled to −78° C., to which 284 mL of sec-BuLi (1 M/L) was added, followed by stirring at the same temperature for 2 hours. 48.7 g of trimethyl borate having been dissolved in 120 mL of THF was added dropwise thereto at the same temperature, followed by stirring at the same temperature for 1 hour, and the mixture was increased in temperature to room temperature and then stirred over night. Under cooling with an ice bath, 200 mL of 3N hydrochloric acid was added to the mixture. The aqueous layer was extracted with diethyl ether, which was added to the organic layer, and the organic layer was washed with a saturated saline and then dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 48.8 g of 2,3-difluoro-5-methylphenylboric acid (3), which was used in the next step without purification. was added was added dropwise by stirring at the same temperature for 1 hour stirred over night Under cooling with an ice bath The aqueous layer was extracted with diethyl ether, which was added to the organic layer the organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate The solvent was distilled off

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

实验步骤: Under a nitrogen atmosphere, 30 g the compound (2) having been dissolved in 240 mL of THF was cooled to −78° C., to which 284 mL of sec-BuLi (1 M/L) was added, followed by stirring at the same temperature for 2 hours. 48.7 g of trimethyl borate having been dissolved in 120 mL of THF was added dropwise thereto at the same temperature, followed by stirring at the same temperature for 1 hour, and the mixture was increased in temperature to room temperature and then stirred over night. Under cooling with an ice bath, 200 mL of 3N hydrochloric acid was added to the mixture. The aqueous layer was extracted with diethyl ether, which was added to the organic layer, and the organic layer was washed with a saturated saline and then dried over anhydrous magnesium sulfate. The solvent was distilled off to obtain 48.8 g of 2,3-difluoro-5-methylphenylboric acid (3), which was used in the next step without purification. was added was added dropwise by stirring at the same temperature for 1 hour stirred over night Under cooling with an ice bath The aqueous layer was extracted with diethyl ether, which was added to the organic layer the organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate The solvent was distilled off

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

实验步骤: Under a nitrogen atmosphere, 82.5 g of 3,4-difluorobromobenzene (1) dissolved in 150 mL of tetrahydrofuran (THF) was added dropwise to 12.5 g of dried magnesium, and after completing the dropwise addition, the mixture was refluxed for 1 hour. The resulting solution was added dropwise to 15 mL of THF having 91.5 g of methyl iodide and 12.3 g of copper(I) iodide added thereto under cooling with an ice bath. After stirring over night, a saturated ammonium chloride aqueous solution was added thereto to terminate the reaction. The aqueous layer was extracted with diethyl ether, which was added to the organic layer, and the organic layer was washed with a saturated saline and then dried over anhydrous magnesium sulfate. The organic layer was distilled to obtain 37.6 g of 2,3-difluorotoluene (2) the dropwise addition the mixture was refluxed for 1 hour added under cooling with an ice bath to terminate the reaction The aqueous layer was extracted with diethyl ether, which was added to the organic layer the organic layer was washed with a saturated saline dried over anhydrous magnesium sulfate The organic layer was distilled

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 4-chloro-3-methyl-4,5,5-trifluorocyclohexene of 58.6 g prepared in Example 12 was added 2.5 g of benzyltriethylammonium chloride, and then the reaction mixture was heated to 80° C. followed by slowly adding 240 g of 50% aqueous sodium hydroxide solution for 1 hour. The reaction mixture was stirred for additional 3 hours at 80° C., and then the resultant was purified by steam distillation followed by separating the aqueous layer. The organic layer was dried with calcium chloride, and then 32.3 g of the desired product was collected by fractional distillation as a colorless liquid. the resultant was purified by steam distillation by separating the aqueous layer The organic layer was dried with calcium chloride 32.3 g of the desired product was collected by fractional distillation as a colorless liquid

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 2.5 M solution of n-butyllithium (3.4 mL, 8.5 mmol) was added to a stirred solution of diisopropylamine (1.2 mL, 8.5 mmol) in THF (25 mL) at −20° C. The resulting solution was stirred at −20° C. for 10 minutes, then cooled to −78° C. A solution of 1,2-difluoro-3-methylbenzene (1.0 g, 7.8 mmol) in THF was added dropwise and stirred at −78° C. for 2 h. 2-Isopropoxy-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (1.6 g, 8.6 mmol) in THF was then added and the brown solution was slowly warmed to 23° C. over 16 hours. The reaction mixture was then added to ether and extracted with water and with 0.1N sodium hydroxide. The combined aqueous extracts were acidified with concentrated HCl then extracted with dichloromethane. The organic phase was dried and concentrated to give the title compound (1.0 g, 50% yield): 1H NMR (CDCl3): δ 7.32 (m, 1H), 6.92 (m, 1H), 2.31 (s, 3H), 1.32 (s, 12H). cooled to −78° C stirred at −78° C. for 2 h the brown solution was slowly warmed to 23° C. over 16 hours extracted with water and with 0.1N sodium hydroxide then extracted with dichloromethane The organic phase was dried concentrated

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

实验步骤: The general procedure was followed using a mixture of 1-(2-propenyl)-2-chloro-2,3,3-trifluorocyclobutane and 1-methyl-1-vinyl-2-chloro-2,3,3-trifluorocyclobutane as the liquid feed at a flow rate of 1 ml/hr. Nitrogen gas was used as the inert carrier. The reactor was charged with 3 g of AL-0104 (tableted activated alumina containing 99% Al2O3). At 400° C. the yield of the produced aromatic products was 12% combined yield of 1-methyl-2,3-difluorobenzene and 1-methyl-3,4-difluorobenzene and a combined yield of 88% of 1-methyl-2-chloro-3-fluorobenzene and 1-methyl-3-chloro-4-fluorobenzene. At 400° C.

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

实验步骤: The general procedure was followed using a mixture of 1-(2-propenyl)-2-chloro-2,3,3-trifluorocyclobutane and 1-methyl-1-vinyl-2-chloro-2,3,3-trifluorocyclobutane as the liquid feed at a flow rate of 1 ml/hr. Nitrogen gas was used as the inert carrier. The reactor was charged with 3 g of AL-0104 (tableted activated alumina containing 99% Al2O3). At 400° C. the yield of the produced aromatic products was 12% combined yield of 1-methyl-2,3-difluorobenzene and 1-methyl-3,4-difluorobenzene and a combined yield of 88% of 1-methyl-2-chloro-3-fluorobenzene and 1-methyl-3-chloro-4-fluorobenzene. At 400° C.

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

实验步骤: To 1,2-difluoro-3-methylbenzene (5 g, 39.0 mmol, commercially available from e.g. Sigma-Aldrich, Apollo or Fluorochem) containing iron (0.131 g, 2.342 mmol) was added bromine (2.011 ml, 39.0 mmol) dropwise maintaining a temperature of <30° C. with ice cooling. The mixture was stirred at room temperature overnight. The mixture was partitioned between water (50 mL) and diethyl ether (100 mL). The aqueous phase was extracted with diethyl ether (3×50 mL), combined organic extracts were washed with water (50 mL), 5% sodium thiosulfate solution (50 mL), water (50 mL), brine (50 mL), dried over anhydrous magnesium sulfate and concentrated in vacuo to afford product in 8.07 g. (Caution: by of product=68-70° C. @ 57 mBar). dropwise maintaining a temperature of <30° C. with ice cooling The mixture was partitioned between water (50 mL) and diethyl ether (100 mL) The aqueous phase was extracted with diethyl ether (3×50 mL) were washed with water (50 mL), 5% sodium thiosulfate solution (50 mL), water (50 mL), brine (50 mL) dried over anhydrous magnesium sulfate concentrated in vacuo to afford product in 8.07 g (Caution: by of product=68-70° C. @ 57 mBar)

反应条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 2.5 M solution of n-butyllithium (3.4 mL, 8.5 mmol) was added to a stirred solution of diisopropylamine (1.2 mL, 8.5 mmol) in THF (25 mL) at −20° C. The resulting solution was stirred at −20° C. for 10 minutes, then cooled to −78° C. A solution of 1,2-difluoro-3-methylbenzene (1.0 g, 7.8 mmol) in THF was added dropwise and stirred at −78° C. for 2 h. 2-Isopropoxy-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (1.6 g, 8.6 mmol) in THF was then added and the brown solution was slowly warmed to 23° C. over 16 hours. The reaction mixture was then added to ether and extracted with water and with 0.1N sodium hydroxide. The combined aqueous extracts were acidified with concentrated HCl then extracted with dichloromethane. The organic phase was dried and concentrated to give the title compound (1.0 g, 50% yield): 1H NMR (CDCl3): δ 7.32 (m, 1H), 6.92 (m, 1H), 2.31 (s, 3H), 1.32 (s, 12H). cooled to −78° C stirred at −78° C. for 2 h the brown solution was slowly warmed to 23° C. over 16 hours extracted with water and with 0.1N sodium hydroxide then extracted with dichloromethane The organic phase was dried concentrated

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a stirred solution of 4-chloro-3-methyl-4,5,5-trifluorocyclohexene of 58.6 g prepared in Example 12 was added 2.5 g of benzyltriethylammonium chloride, and then the reaction mixture was heated to 80° C. followed by slowly adding 240 g of 50% aqueous sodium hydroxide solution for 1 hour. The reaction mixture was stirred for additional 3 hours at 80° C., and then the resultant was purified by steam distillation followed by separating the aqueous layer. The organic layer was dried with calcium chloride, and then 32.3 g of the desired product was collected by fractional distillation as a colorless liquid. the resultant was purified by steam distillation by separating the aqueous layer The organic layer was dried with calcium chloride 32.3 g of the desired product was collected by fractional distillation as a colorless liquid