2-Benzyloxy-5-chlorobenzeneboronic acid

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyllithium (11.5 ml, 28.7 mmol, 2.5 M) was added, under nitrogen, over 10 minutes, to a solution of 2-benzyloxy-5-chloro-iodobenzene (9 g, 26.2 mmol) in THF (40 ml) at −100° C. The reaction mixture was then warmed up at −78° C. and stirred for 1 hour (at −78° C.) before triisopropyl borate (18 ml, 78.4 mmol) was added over 10 minutes. The reaction mixture was then warmed to room temperature before a solution of HCl (60 ml, 1M) was added. The mixture was vigorously stirred for 1½ hours. The organic phase was separated, washed sequentially with water and brine, dried (MgSO4) filtered and concentrated. The residue was triturated with a 30% solution of ether in iso-hexane and filtered to give the title compound (3.62 g, 53%) as a white solid. was added over 10 minutes was added The organic phase was separated washed sequentially with water and brine dried (MgSO4) filtered concentrated The residue was triturated with a 30% solution of ether in iso-hexane filtered

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyllithium (11.5 ml, 28.7 mmol, 2.5 M) was added, under nitrogen, over 10 minutes, to a solution of 2-benzyloxy-5-chloro-iodobenzene (9 g, 26.2 mmol) in THF (40 ml) at −100° C. The reaction mixture was then warmed up at −78° C. and stirred for 1 hour (at −78° C.) before triisopropyl borate (18 ml, 78.4 mmol) was added over 10 minutes. The reaction mixture was then warmed to room temperature before a solution of HCl (60 ml, 1M) was added. The mixture was vigorously stirred for 1½ hours. The organic phase was separated, washed sequentially with water and brine, dried (MgSO4) filtered and concentrated. The residue was triturated with a 30% solution of ether in iso-hexane and filtered to give the title compound (3.62 g, 53%) as a white solid. was added over 10 minutes was added The organic phase was separated washed sequentially with water and brine dried (MgSO4) filtered concentrated The residue was triturated with a 30% solution of ether in iso-hexane filtered

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

Procedure: A mixture of 5-(2′-bromo-biphenyl-3-yl)-1H-tetrazole (163 mg, 0.54 mmol), 2-benzyloxy-5-chlorobenzeneboronic acid (156 mg, 0.59 mmol), potassium carbonate (589 mg, 4.33 mmol), and tetrakis(triphenylphosphine)palladium(0) (63 mg, 0.05 mmol) in 1.1 toluene/ethanol (5 ml) was stirred and heated under nitrogen for 16 hours. After cooling the mixture was diluted with dichloromethane and water. The organic phase was dried and evaporated. heated under nitrogen for 16 hours After cooling the mixture The organic phase was dried evaporated

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

Procedure: A mixture of 5-(2′-bromo-biphenyl-3-yl)-1H-tetrazole (163 mg, 0.54 mmol), 2-benzyloxy-5-chlorobenzeneboronic acid (156 mg, 0.59 mmol), potassium carbonate (589 mg, 4.33 mmol), and tetrakis(triphenylphosphine)palladium(0) (63 mg, 0.05 mmol) in 1.1 toluene/ethanol (5 ml) was stirred and heated under nitrogen for 16 hours. After cooling the mixture was diluted with dichloromethane and water. The organic phase was dried and evaporated. heated under nitrogen for 16 hours After cooling the mixture The organic phase was dried evaporated

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-benzyloxy-5-chloro-phenyl-boronic acid (197 mg, 0.75 mmol), 5-amino-2′-bromo-biphenyl-3-carboxylic acid methyl ester (216 mg, 0.71 mmol), potassium carbonate (828 mg, 6 mmol) and tetrakis(triphenylphosphine)palladium(0) (79 mg, 0.068 mmol) in 1:1 toluene/ethanol (8 ml) was stirred and heated at 90° C. under nitrogen for 2 hours. After cooling the mixture was diluted with diethyl ether and water and the organic phase dried (MgSO4) and evaporated to dryness. The residue was purified using Biotage with ethyl acetate/iso-hexane (1:4) to yield the title compound as a pale yellow gum. (288 mg, 89%). After cooling the mixture the organic phase dried (MgSO4) evaporated to dryness The residue was purified

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-benzyloxy-5-chloro-phenyl-boronic acid (197 mg, 0.75 mmol), 5-amino-2′-bromo-biphenyl-3-carboxylic acid methyl ester (216 mg, 0.71 mmol), potassium carbonate (828 mg, 6 mmol) and tetrakis(triphenylphosphine)palladium(0) (79 mg, 0.068 mmol) in 1:1 toluene/ethanol (8 ml) was stirred and heated at 90° C. under nitrogen for 2 hours. After cooling the mixture was diluted with diethyl ether and water and the organic phase dried (MgSO4) and evaporated to dryness. The residue was purified using Biotage with ethyl acetate/iso-hexane (1:4) to yield the title compound as a pale yellow gum. (288 mg, 89%). After cooling the mixture the organic phase dried (MgSO4) evaporated to dryness The residue was purified

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

Procedure: 2′-Bromo-biphenyl-3-carboxylic acid ethyl ester (157 mg, 0.5 mmol), 2-benzyloxy-5-chloro-phenylboronic acid (157 mg, 0.6 mmol), tetrakis(triphenylphosphine)palladium(0) (66 mg, 0.06 mmol) and potassium carbonate (568 mg, 4.1 mmol) was heated in toluene-ethanol (1:1, 5 ml) at 90° C. for 4.5 hours. Upon cooling, the mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by chromatography using Biotage with iso-hexane containing a gradient of ethyl acetate (1-5%) to yield the title compound (105 mg, 46%) as a white solid. Upon cooling The layers were separated the aqueous phase was extracted with ethyl acetate The combined extracts were dried (Na2SO4) filtered concentrated The residue was purified by chromatography

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

Procedure: 2′-Bromo-biphenyl-3-carboxylic acid ethyl ester (157 mg, 0.5 mmol), 2-benzyloxy-5-chloro-phenylboronic acid (157 mg, 0.6 mmol), tetrakis(triphenylphosphine)palladium(0) (66 mg, 0.06 mmol) and potassium carbonate (568 mg, 4.1 mmol) was heated in toluene-ethanol (1:1, 5 ml) at 90° C. for 4.5 hours. Upon cooling, the mixture was diluted with ethyl acetate and water. The layers were separated and the aqueous phase was extracted with ethyl acetate. The combined extracts were dried (Na2SO4), filtered and concentrated. The residue was purified by chromatography using Biotage with iso-hexane containing a gradient of ethyl acetate (1-5%) to yield the title compound (105 mg, 46%) as a white solid. Upon cooling The layers were separated the aqueous phase was extracted with ethyl acetate The combined extracts were dried (Na2SO4) filtered concentrated The residue was purified by chromatography

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

Procedure: Pinacol (3.24 g) was added to a solution of [5-chloro-2-(phenylmethoxy)phenyl]-boronic acid (6 g) in diethyl ether, and stirred for 24 h. 4A molecular sieves and pinacol (1.5 g) were added, stirred for a further 24 h. The sieves were filtered and the filtrate was washed with water and brine, then dried (MgSO4) and concentrated in vacuo. Yield 6.8 g. stirred for a further 24 h The sieves were filtered the filtrate was washed with water and brine dried (MgSO4) concentrated in vacuo

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

Procedure: The sub-title compound was prepared by the method of Example 11 step b) using the product of step b) and [5-chloro-2-(phenylmethoxy)phenyl]boronic acid. M.p. 143-4° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Butyllithium (11.5 ml, 28.7 mmol, 2.5 M) was added, under nitrogen, over 10 minutes, to a solution of 2-benzyloxy-5-chloro-iodobenzene (9 g, 26.2 mmol) in THF (40 ml) at −100° C. The reaction mixture was then warmed up at −78° C. and stirred for 1 hour (at −78° C.) before triisopropyl borate (18 ml, 78.4 mmol) was added over 10 minutes. The reaction mixture was then warmed to room temperature before a solution of HCl (60 ml, 1M) was added. The mixture was vigorously stirred for 1½ hours. The organic phase was separated, washed sequentially with water and brine, dried (MgSO4) filtered and concentrated. The residue was triturated with a 30% solution of ether in iso-hexane and filtered to give the title compound (3.62 g, 53%) as a white solid. was added over 10 minutes was added The organic phase was separated washed sequentially with water and brine dried (MgSO4) filtered concentrated The residue was triturated with a 30% solution of ether in iso-hexane filtered