tert-butyl 5-bromo-2-chlorobenzoate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., isobutylmagnesium bromide (2.0 M ether solution, 1.2 eq.) and n-butyl lithium (2.5 M hexane solution, 2.4 eq.) were added to anhydrous THF (0.3 M). After stirring at 0° C. for 30 min, the reaction mixture was cooled to −40° C. and tert-butyl 5-bromo-2-chlorobenzoate from the previous step (1 eq.) was added over 15 min. The now red solution was stirred at −40° C. for 1 h before copper (I) cyanide (30% loading) was added. The resulting suspension was stirred at −40° C. for 15 min and then added allyl bromide (3 eq.). After stirring at −40° C. for another 2 h, the reaction mixture was quenched with sat. aq. NH4Cl and warmed to RT. The biphasic mixture was poured into more sat. aq. NH4Cl and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a brown oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→19:1 (v/v) Hex:ether) afforded the title compound as a light yellow oil. the reaction mixture was cooled to −40° C. was added The resulting suspension was stirred at −40° C. for 15 min After stirring at −40° C. for another 2 h the reaction mixture was quenched with sat. aq. NH4Cl warmed to RT The biphasic mixture was poured into more sat. aq. NH4Cl extracted with ether The combined organic extracts were washed with brine dried over MgSO4 filtered Concentration of the filtrate in vacuo afforded a brown oil Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→19:1 (v/v) Hex:ether)

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 0° C., isobutylmagnesium bromide (2.0 M ether solution, 1.2 eq.) and n-butyl lithium (2.5 M hexane solution, 2.4 eq.) were added to anhydrous THF (0.3 M). After stirring at 0° C. for 30 min, the reaction mixture was cooled to −40° C. and tert-butyl 5-bromo-2-chlorobenzoate from the previous step (1 eq.) was added over 15 min. The now red solution was stirred at −40° C. for 1 h before copper (I) cyanide (30% loading) was added. The resulting suspension was stirred at −40° C. for 15 min and then added allyl bromide (3 eq.). After stirring at −40° C. for another 2 h, the reaction mixture was quenched with sat. aq. NH4Cl and warmed to RT. The biphasic mixture was poured into more sat. aq. NH4Cl and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a brown oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→19:1 (v/v) Hex:ether) afforded the title compound as a light yellow oil. the reaction mixture was cooled to −40° C. was added The resulting suspension was stirred at −40° C. for 15 min After stirring at −40° C. for another 2 h the reaction mixture was quenched with sat. aq. NH4Cl warmed to RT The biphasic mixture was poured into more sat. aq. NH4Cl extracted with ether The combined organic extracts were washed with brine dried over MgSO4 filtered Concentration of the filtrate in vacuo afforded a brown oil Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→19:1 (v/v) Hex:ether)

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

実験手順: 5-bromo-2-chlorobenzoic acid (1 eq.) and anhydrous DMF (1.2 eq.) was taken up in toluene (0.9 M). To this was then added, dropwise over 5 min, oxalyl chloride (1.2 eq.) and the reaction mixture was stirred at RT for 1 h. The volatiles were then removed in vacuo and the resulting residue was taken up in toluene (0.9 M). At 0° C., potassium tert-butoxide (2.5 eq.) was added and the reaction mixture was stirred at RT for 1 h. The reaction mixture was poured into H2O and extracted with ether. The combined organic extracts were washed with brine, dried over MgSO4 and filtered. Concentration of the filtrate in vacuo afforded a pale yellow oil. Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→85:15 (v/v) Hex:EtOAc) afforded the title compound as a light yellow oil. To this was then added, dropwise over 5 min The volatiles were then removed in vacuo extracted with ether The combined organic extracts were washed with brine dried over MgSO4 filtered Concentration of the filtrate in vacuo afforded a pale yellow oil Purification of the crude product thus obtained by way of flash chromatography (SiO2, Hex→85:15 (v/v) Hex:EtOAc)

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chlorobenzoic acid (11.75 g) in N,N-dimethylformamide (50 ml) was added 1,1′-carbonyldiimidazole (8.10 g), and the mixture was stirred under heating at 40° C. for one hour. Thereto were added t-butanol (7.40 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (7.60 g), and the mixture was further stirred under heating at 40° C. overnight. The mixture was diluted with diethyl ether, and washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give t-butyl 5-bromo-2-chlorobenzoate (12.53 g) as pale yellow oil. the mixture was further stirred under heating at 40° C. overnight washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine The mixture was dried over magnesium sulfate the solvent was evaporated under reduced pressure

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chlorobenzoic acid (11.75 g) in N,N-dimethylformamide (50 ml) was added 1,1′-carbonyldiimidazole (8.10 g), and the mixture was stirred under heating at 40° C. for one hour. Thereto were added t-butanol (7.40 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (7.60 g), and the mixture was further stirred under heating at 40° C. overnight. The mixture was diluted with diethyl ether, and washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give t-butyl 5-bromo-2-chlorobenzoate (12.53 g) as pale yellow oil. the mixture was further stirred under heating at 40° C. overnight washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine The mixture was dried over magnesium sulfate the solvent was evaporated under reduced pressure

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chlorobenzoic acid (11.75 g) in N,N-dimethylformamide (50 ml) was added 1,1′-carbonyldiimidazole (8.10 g), and the mixture was stirred under heating at 40° C. for one hour. Thereto were added t-butanol (7.40 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (7.60 g), and the mixture was further stirred under heating at 40° C. overnight. The mixture was diluted with diethyl ether, and washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give t-butyl 5-bromo-2-chlorobenzoate (12.53 g) as pale yellow oil. the mixture was further stirred under heating at 40° C. overnight washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine The mixture was dried over magnesium sulfate the solvent was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: tert-Butyl 5-bromo-2-chlorobenzoate (1.9 g) (WO2003095430) was dissolved in methanol (18 ml) with N,N-diisopropylethylamine (2 mL) and dichlorobis(triphenylphosphine)-palladium(II) (0.134 g). The mixture was carbonylated at 85° C. for 12 h. The cooled solution was evaporated and purified by flash chromatography, eluting with 5:95 ethyl acetate/isohexane, to yield the subtitle compound as a colourless oil (0.67 g). The cooled solution was evaporated purified by flash chromatography eluting with 5:95 ethyl acetate/isohexane

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

実験手順: tert-Butyl 5-bromo-2-chlorobenzoate (1.9 g) (WO2003095430) was dissolved in methanol (18 ml) with N,N-diisopropylethylamine (2 mL) and dichlorobis(triphenylphosphine)-palladium(II) (0.134 g). The mixture was carbonylated at 85° C. for 12 h. The cooled solution was evaporated and purified by flash chromatography, eluting with 5:95 ethyl acetate/isohexane, to yield the subtitle compound as a colourless oil (0.67 g). The cooled solution was evaporated purified by flash chromatography eluting with 5:95 ethyl acetate/isohexane

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

実験手順: tert-Butyl 5-bromo-2-chlorobenzoate (1.9 g) (WO2003095430) was dissolved in methanol (18 ml) with N,N-diisopropylethylamine (2 mL) and dichlorobis(triphenylphosphine)-palladium(II) (0.134 g). The mixture was carbonylated at 85° C. for 12 h. The cooled solution was evaporated and purified by flash chromatography, eluting with 5:95 ethyl acetate/isohexane, to yield the subtitle compound as a colourless oil (0.67 g). The cooled solution was evaporated purified by flash chromatography eluting with 5:95 ethyl acetate/isohexane

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 5-bromo-2-chlorobenzoic acid (11.75 g) in N,N-dimethylformamide (50 ml) was added 1,1′-carbonyldiimidazole (8.10 g), and the mixture was stirred under heating at 40° C. for one hour. Thereto were added t-butanol (7.40 g) and 1,8-diazabicyclo[5.4.0]undec-7-ene (7.60 g), and the mixture was further stirred under heating at 40° C. overnight. The mixture was diluted with diethyl ether, and washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine. The mixture was dried over magnesium sulfate, and the solvent was evaporated under reduced pressure to give t-butyl 5-bromo-2-chlorobenzoate (12.53 g) as pale yellow oil. the mixture was further stirred under heating at 40° C. overnight washed successively with water (3 times), 2% aqueous hydrochloric acid solution (twice), a saturated aqueous sodium hydrogen carbonate solution and brine The mixture was dried over magnesium sulfate the solvent was evaporated under reduced pressure