1-bromo-2-fluoro-3-(trifluoromethyl)benzene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine 1-bromo-2-fluoro-3-trifluoromethylbenzene (0.424 g, 1.77 mmol), 5,5,5′,5′-tetramethyl-[2,2′]bi[1,3,2]dioxaborinanyl] (0.458 g, 2.03 mmol), 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium (0.0632 g, 0.0774 mmol), and potassium acetate (0.499 g, 5.08 mmol) in DMF (10 mL), and purge with nitrogen for 0.5 hr. Heat for 2 hr. at 80° C. and cool to room temperature. Add 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.406 g, 1.36 mmol), sodium carbonate (4.0 mL of a 2M solution in water,) and bis(diphenylphosphino)ferrocene dichloropalladium (0.052 g, 0.0638 mmol). Heat the reaction at 80° C. for 20 hr. Purify by silica gel chromatography, eluting with 5:95 to 40:60 ethyl acetate:hexanes to give the 3′-(2-fluoro-3-trifluoromethyl-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.102 g, 18%). Heat for 2 hr Heat the reaction at 80° C. for 20 hr Purify by silica gel chromatography eluting with 5:95 to 40:60 ethyl acetate

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine 1-bromo-2-fluoro-3-trifluoromethylbenzene (0.424 g, 1.77 mmol), 5,5,5′,5′-tetramethyl-[2,2′]bi[1,3,2]dioxaborinanyl] (0.458 g, 2.03 mmol), 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium (0.0632 g, 0.0774 mmol), and potassium acetate (0.499 g, 5.08 mmol) in DMF (10 mL), and purge with nitrogen for 0.5 hr. Heat for 2 hr. at 80° C. and cool to room temperature. Add 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.406 g, 1.36 mmol), sodium carbonate (4.0 mL of a 2M solution in water,) and bis(diphenylphosphino)ferrocene dichloropalladium (0.052 g, 0.0638 mmol). Heat the reaction at 80° C. for 20 hr. Purify by silica gel chromatography, eluting with 5:95 to 40:60 ethyl acetate:hexanes to give the 3′-(2-fluoro-3-trifluoromethyl-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.102 g, 18%). Heat for 2 hr Heat the reaction at 80° C. for 20 hr Purify by silica gel chromatography eluting with 5:95 to 40:60 ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzotrifluoride (1.72 g, 7.1 mmol) in toluene (50 ml) under nitrogen, was added piperazine (0.89 g, 10.6 mmol), potassium tert-butoxide (0.95 g, 9.9 mmol), bis(dibenzylideneacetone)palladium(0) (0.19 g, 0.21 mmol) and (+/−)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (0.13 g, 0.21 mmol). The resulting mixture was heated at 80° C. for 20 h. Filtration through a pad of celite and evaporation of the filtrate gave 2.1 g of crude product. The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (0.96 g). MS m/z (rel. intensity, 70 eV) 248 (M+, 23), 207 (10), 206 (bp), 190 (17), 163 (8). Filtration through a pad of celite and evaporation of the filtrate gave 2.1 g of crude product The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzotrifluoride (1.0 g, 4.1 mmol) in methanol (5 ml) was added a solution of sodium methoxide in methanol (30%, 0.73 ml, 4.1 mmol). The mixture was heated under microwave radiation to 150° C. for 10 min. The reaction mixture was poured into water and extracted with ethylacetate (3×50 ml). The combined organic phases was dried (MgSO4), filtered and evaporated to dryness to give the title compound (0.89 g). MS m/z (rel. intensity, 70 eV) 256 (M+, 87), 254 (M+, 89), 239 (26), 211 (24), 132 (bp). extracted with ethylacetate (3×50 ml) The combined organic phases was dried (MgSO4) filtered evaporated to dryness

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzotrifluoride (1.0 g, 4.1 mmol) in methanol (5 ml) was added a solution of sodium methoxide in methanol (30%, 0.73 ml, 4.1 mmol). The mixture was heated under microwave radiation to 150° C. for 10 min. The reaction mixture was poured into water and extracted with ethylacetate (3×50 ml). The combined organic phases was dried (MgSO4), filtered and evaporated to dryness to give the title compound (0.89 g). MS m/z (rel. intensity, 70 eV) 256 (M+, 87), 254 (M+, 89), 239 (26), 211 (24), 132 (bp). extracted with ethylacetate (3×50 ml) The combined organic phases was dried (MgSO4) filtered evaporated to dryness

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzotrifluoride (1.72 g, 7.1 mmol) in toluene (50 ml) under nitrogen, was added piperazine (0.89 g, 10.6 mmol), potassium tert-butoxide (0.95 g, 9.9 mmol), b is (dibenzylideneacetone)palladium(0) (0.19 g, 0.21 mmol) and (+/−)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (0.13 g, 0.21 mmol). The resulting mixture was heated at 80° C. for 20 h. Filtration through a pad of celite and evaporation of the filtrate gave 2.1 g of crude product. The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (0.96 g). MS m/z (rel. intensity, 70 eV) 248 (M+, 23), 207 (10), 206 (bp), 190 (17), 163 (8). Filtration through a pad of celite and evaporation of the filtrate gave 2.1 g of crude product The residue was purified by flash column chromatography (ethylacetate/methanol, 1:1)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-bromo-2-fluorobenzotrifluoride (1.0 g, 4.1 mmol) in methanol (5 ml) was added a solution of sodium methoxide in methanol (30%, 0.73 ml, 4.1 mmol). The mixture was heated under microwave radiation to 150° C. for 10 min. The reaction mixture was poured into water and extracted with ethylacetate (3×50 ml). The combined organic phases was dried (MgSO4), filtered and evaporated to dryness to give the title compound (0.89 g). MS m/z (rel. intensity, 70 eV) 256 (M+, 87), 254 (M+, 89), 239 (26), 211 (24), 132 (bp). extracted with ethylacetate (3×50 ml) The combined organic phases was dried (MgSO4) filtered evaporated to dryness

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Combine 1-bromo-2-fluoro-3-trifluoromethylbenzene (0.424 g, 1.77 mmol), 5,5,5′,5′-tetramethyl-[2,2′]bi[1,3,2]dioxaborinanyl] (0.458 g, 2.03 mmol), 1,1′-bis(diphenylphosphino)ferrocene dichloropalladium (0.0632 g, 0.0774 mmol), and potassium acetate (0.499 g, 5.08 mmol) in DMF (10 mL), and purge with nitrogen for 0.5 hr. Heat for 2 hr. at 80° C. and cool to room temperature. Add 3′-chloro-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.406 g, 1.36 mmol), sodium carbonate (4.0 mL of a 2M solution in water,) and bis(diphenylphosphino)ferrocene dichloropalladium (0.052 g, 0.0638 mmol). Heat the reaction at 80° C. for 20 hr. Purify by silica gel chromatography, eluting with 5:95 to 40:60 ethyl acetate:hexanes to give the 3′-(2-fluoro-3-trifluoromethyl-phenyl)-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid t-butyl ester (0.102 g, 18%). Heat for 2 hr Heat the reaction at 80° C. for 20 hr Purify by silica gel chromatography eluting with 5:95 to 40:60 ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir: