2,5-dibromo-1,3-dimethylbenzene

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,5-dibromo-1,3-dimethylbenzene (2.00 g), 1-furan-3-ylboronic acid (856 mg), and 2 M aqueous Na2CO3 solution (11 mL) in 1,4-dioxane (40 mL) is purged with argon for 5 min. Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added and the mixture is stirred at 100° C. over night. More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added and the mixture is stirred for another 5 h at 100° C. After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution. The aqueous phase is extracted with ethyl acetate and the combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10) to give the title compound. LC (method 7): tR=1.22 min; Mass spectrum (EI+): m/z=250 [M]+. is purged with argon for 5 min Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added the mixture is stirred for another 5 h at 100° C After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution The aqueous phase is extracted with ethyl acetate the combined extracts are washed with brine dried over MgSO4 concentrated in vacuo The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a microwave vial 2,5-dibromo-1,3-dimethylbenzene (800 mg), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (640 mg) and K3PO4 (1.3 g) are suspended in toluene (12 mL) and water (1.2 mL) and purged for 10 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added, the vial is sealed and the mixture is stirred at 60° C. for 12 hours. After cooling to room temperature the mixture is diluted with diethylether and washed with saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40) to give the title compound. Yield: 404 mg. water (1.2 mL) and purged for 10 minutes with argon [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added the vial is sealed After cooling to room temperature the mixture is diluted with diethylether washed with saturated aqueous NH4Cl solution The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of isopropylmagnesium chloride (6.15 mL of a 2 M solution in tetrahydrofurane) in tetrahydrofurane (75 mL) is added dropwise at 0° C. n-butyllithium (15.4 mL of a 1.6 M solution in n-hexane). The mixture is stirred for 10 minutes, a solution of 2,5-dibromo-1,3-dimethylbenzene (5 g) in tetrahydrofurane (75 mL) is added within 10 minutes. The mixture is stirred for 2 hours, cooled to −40° C. and then CuCN×LiCl (5.5 mL of a 1 M solution in tetrahydrofurane) is added dropwise. After stirring for 5 minutes 3-bromopropene (6.6 mL) is added dropwise, the mixture is stirred for 1 hour, warmed to room temperature and stirred for further 12 hours. Then the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether, the organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (dichloromethane) to give the title compound. Yield: 3.76 g; LC (method 8): tR=0.83 min; Mass spectrum (ESI+): m/z=225 [M+H]+. The mixture is stirred for 2 hours is added dropwise the mixture is stirred for 1 hour warmed to room temperature stirred for further 12 hours Then the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether the organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,5-dibromo-1,3-dimethylbenzene (500 mg) in diethylether (3 mL) and tetrahydrofuran (2.5 mL) is cooled to −78° C. and treated dropwise with n-butyllithium (200 μL of a 10 M solution in n-hexane). The mixture is stirred for 1 hour and treated dropwise with chloro-trimethyl-silane (275 μL). After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10) to give the title compound. Yield: 260 mg; Mass spectrum (ESI+): m/z=279 [M+Na]+. After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,5-dibromo-1,3-dimethylbenzene (2.00 g), 1-furan-3-ylboronic acid (856 mg), and 2 M aqueous Na2CO3 solution (11 mL) in 1,4-dioxane (40 mL) is purged with argon for 5 min. Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added and the mixture is stirred at 100° C. over night. More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added and the mixture is stirred for another 5 h at 100° C. After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution. The aqueous phase is extracted with ethyl acetate and the combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10) to give the title compound. LC (method 7): tR=1.22 min; Mass spectrum (EI+): m/z=250 [M]+. is purged with argon for 5 min Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added the mixture is stirred for another 5 h at 100° C After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution The aqueous phase is extracted with ethyl acetate the combined extracts are washed with brine dried over MgSO4 concentrated in vacuo The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a microwave vial 2,5-dibromo-1,3-dimethylbenzene (800 mg), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (640 mg) and K3PO4 (1.3 g) are suspended in toluene (12 mL) and water (1.2 mL) and purged for 10 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added, the vial is sealed and the mixture is stirred at 60° C. for 12 hours. After cooling to room temperature the mixture is diluted with diethylether and washed with saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40) to give the title compound. Yield: 404 mg. water (1.2 mL) and purged for 10 minutes with argon [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added the vial is sealed After cooling to room temperature the mixture is diluted with diethylether washed with saturated aqueous NH4Cl solution The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of isopropylmagnesium chloride (6.15 mL of a 2 M solution in tetrahydrofurane) in tetrahydrofurane (75 mL) is added dropwise at 0° C. n-butyllithium (15.4 mL of a 1.6 M solution in n-hexane). The mixture is stirred for 10 minutes, a solution of 2,5-dibromo-1,3-dimethylbenzene (5 g) in tetrahydrofurane (75 mL) is added within 10 minutes. The mixture is stirred for 2 hours, cooled to −40° C. and then CuCN×LiCl (5.5 mL of a 1 M solution in tetrahydrofurane) is added dropwise. After stirring for 5 minutes 3-bromopropene (6.6 mL) is added dropwise, the mixture is stirred for 1 hour, warmed to room temperature and stirred for further 12 hours. Then the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether, the organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (dichloromethane) to give the title compound. Yield: 3.76 g; LC (method 8): tR=0.83 min; Mass spectrum (ESI+): m/z=225 [M+H]+. The mixture is stirred for 2 hours is added dropwise the mixture is stirred for 1 hour warmed to room temperature stirred for further 12 hours Then the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether the organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,5-dibromo-1,3-dimethylbenzene (500 mg) in diethylether (3 mL) and tetrahydrofuran (2.5 mL) is cooled to −78° C. and treated dropwise with n-butyllithium (200 μL of a 10 M solution in n-hexane). The mixture is stirred for 1 hour and treated dropwise with chloro-trimethyl-silane (275 μL). After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10) to give the title compound. Yield: 260 mg; Mass spectrum (ESI+): m/z=279 [M+Na]+. After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2,5-dibromo-1,3-dimethylbenzene (2.00 g), 1-furan-3-ylboronic acid (856 mg), and 2 M aqueous Na2CO3 solution (11 mL) in 1,4-dioxane (40 mL) is purged with argon for 5 min. Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added and the mixture is stirred at 100° C. over night. More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added and the mixture is stirred for another 5 h at 100° C. After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution. The aqueous phase is extracted with ethyl acetate and the combined extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10) to give the title compound. LC (method 7): tR=1.22 min; Mass spectrum (EI+): m/z=250 [M]+. is purged with argon for 5 min Tetrakis-triphenylphosphine-palladium-(0) (270 mg) is added More tetrakis-triphenylphosphine-palladium-(0) (50 mg) is added the mixture is stirred for another 5 h at 100° C After cooling to room temperature the mixture is diluted with ethyl acetate and aqueous NH4Cl solution The aqueous phase is extracted with ethyl acetate the combined extracts are washed with brine dried over MgSO4 concentrated in vacuo The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 100:0→90:10)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a microwave vial 2,5-dibromo-1,3-dimethylbenzene (800 mg), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (640 mg) and K3PO4 (1.3 g) are suspended in toluene (12 mL) and water (1.2 mL) and purged for 10 minutes with argon. [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added, the vial is sealed and the mixture is stirred at 60° C. for 12 hours. After cooling to room temperature the mixture is diluted with diethylether and washed with saturated aqueous NH4Cl solution. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40) to give the title compound. Yield: 404 mg. water (1.2 mL) and purged for 10 minutes with argon [1,1′-Bis(diphenylphosphino)-ferrocene]-dichloropalladium-(II) (100 mg) is added the vial is sealed After cooling to room temperature the mixture is diluted with diethylether washed with saturated aqueous NH4Cl solution The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→60:40)

Conditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of isopropylmagnesium chloride (6.15 mL of a 2 M solution in tetrahydrofurane) in tetrahydrofurane (75 mL) is added dropwise at 0° C. n-butyllithium (15.4 mL of a 1.6 M solution in n-hexane). The mixture is stirred for 10 minutes, a solution of 2,5-dibromo-1,3-dimethylbenzene (5 g) in tetrahydrofurane (75 mL) is added within 10 minutes. The mixture is stirred for 2 hours, cooled to −40° C. and then CuCN×LiCl (5.5 mL of a 1 M solution in tetrahydrofurane) is added dropwise. After stirring for 5 minutes 3-bromopropene (6.6 mL) is added dropwise, the mixture is stirred for 1 hour, warmed to room temperature and stirred for further 12 hours. Then the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether, the organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (dichloromethane) to give the title compound. Yield: 3.76 g; LC (method 8): tR=0.83 min; Mass spectrum (ESI+): m/z=225 [M+H]+. The mixture is stirred for 2 hours is added dropwise the mixture is stirred for 1 hour warmed to room temperature stirred for further 12 hours Then the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether the organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (dichloromethane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2,5-dibromo-1,3-dimethylbenzene (500 mg) in diethylether (3 mL) and tetrahydrofuran (2.5 mL) is cooled to −78° C. and treated dropwise with n-butyllithium (200 μL of a 10 M solution in n-hexane). The mixture is stirred for 1 hour and treated dropwise with chloro-trimethyl-silane (275 μL). After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution. The mixture is extracted with diethylether. The organic phase is dried (MgSO4) and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10) to give the title compound. Yield: 260 mg; Mass spectrum (ESI+): m/z=279 [M+Na]+. After stirring for 2 hours the reaction is quenched by addition of saturated aqueous NH4Cl solution The mixture is extracted with diethylether The organic phase is dried (MgSO4) concentrated The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 99:1→90:10)