(5-chloro-2-methoxyphenyl)boronic acid

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

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

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

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

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

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

Procedure: A stirred mixture of 5.7 grams (0.020 mole) of 5-chloro-2-methoxyphenylboronic acid, 3.3 grams (0.014 mole) of 2-amino-5-bromo-6-chlorobenzonitrile (prepared in Step A of this Example), 21 mL of aqueous 2M sodium carbonate, and 0.15 gram (catalyst) of tetrakis(triphenylphosphine)palladium(0) in 50 mL of toluene was heated at reflux for about 17 hours. After this time, 50 mL of ethyl acetate was added to the reaction mixture. The organic layer was separated and washed with 50 mL of water and then with 50 mL of an aqueous solution saturated with sodium chloride. The organic layer was then dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue. The residue was subjected to column chromatography on silica gel. Elution was accomplished using methylene chloride. The product-containing fractions were combined and concentrated under reduced pressure, yielding 3.8 grams of 2-amino-6-chloro-5-(5-chloro-2-methoxyphenyl)benzonitrile. The NMR spectrum was consistent with the proposed structure. was heated at reflux for about 17 hours The organic layer was separated washed with 50 mL of water The organic layer was then dried with magnesium sulfate filtered The filtrate was concentrated under reduced pressure to a residue Elution concentrated under reduced pressure

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A stirred solution of 5.8 grams (0.026 mole) of 3-bromo-4-methoxychlorobenzene in 150 mL of tetrahydrofuran was cooled to -80° C., and 11.5 mL of n-butyllithium in hexanes (2.5 Molar-0.029 mole) was added dropwise during a 15 minute period, while maintaining the reaction mixture temperature at about -70° C. The initial reaction was very exothermic, which required cooling the reaction mixture to about -100° C. Upon completion of the addition, the reaction mixture was stirred at -80° C. for 15 minutes. After this time, 17.5 mL (0.076 mole) triisopropyl borate was added during a 1 minute period. The reaction mixture was then allowed to warm slowly to ambient temperature during a 3 hour period, where it was stirred for an additional 1 hour. After this time, the reaction mixture was concentrated under reduced pressure to a volume of about 50 mL. The concentrate was then poured into 500 mL of ice-water. The mixture was then made acidic with about 26 mL of aqueous 2N hydrochloric acid. The mixture was then filtered to collect a solid, which was dried, yielding 3.9 grams of 5-chloro-2-methoxyphenylboronic acid. The NMR spectrum was consistent with the proposed structure. The initial reaction which required cooling the reaction mixture to about -100° C Upon completion of the addition to warm slowly to ambient temperature during a 3 hour period where it was stirred for an additional 1 hour After this time, the reaction mixture was concentrated under reduced pressure to a volume of about 50 mL The concentrate was then poured into 500 mL of ice-water The mixture was then filtered to collect a solid, which was dried

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-bromo-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 9, 3.75 g, 11.5 mmol), 5-chloro-2-methoxyphenylboronic acid (2.57 g, 13.8 mmol), cessium carbonate (7.49 g, 23.0 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.33 g, 1.16 mmol) was suspended in anhydrous N,N-dimethylformamide (70 ml) and stirred at 80° C. overnight under argon atmosphere. After cooling down, ethyl acetate (300 mL), diethylether (150 mL) and water (400 mL) were added and partitioned. The organic layer was washed with water (250 mL) and saturated brine (150 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (3.84 g) as a colorless amorphous product. (Yield 86%) After cooling down partitioned The organic layer was washed with water (250 mL) and saturated brine (150 mL) successively dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 7-bromo-8-methoxycarbonyl-1,3,3-trimethyl-3,4-dihydro-1H-quinoxalin-2-one (Reference Compound No. 9, 3.75 g, 11.5 mmol), 5-chloro-2-methoxyphenylboronic acid (2.57 g, 13.8 mmol), cessium carbonate (7.49 g, 23.0 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.33 g, 1.16 mmol) was suspended in anhydrous N,N-dimethylformamide (70 ml) and stirred at 80° C. overnight under argon atmosphere. After cooling down, ethyl acetate (300 mL), diethylether (150 mL) and water (400 mL) were added and partitioned. The organic layer was washed with water (250 mL) and saturated brine (150 mL) successively, dried over anhydrous magnesium sulfate, and then the solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate) to give the titled reference compound (3.84 g) as a colorless amorphous product. (Yield 86%) After cooling down partitioned The organic layer was washed with water (250 mL) and saturated brine (150 mL) successively dried over anhydrous magnesium sulfate the solvent was removed under reduced pressure The obtained residue was purified by silica gel column chromatography (hexane-ethyl acetate)

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

Procedure: A solution of 5-chloro-2-methoxy benzeneboronic acid (1.9 g, 10 mmol) in hydrogen peroxide (2.04 ml, 30% solution) and ethanol 40 ml was refluxed for 30 min. Water was added and the product was extracted with two portions of ethyiacetate. Drying over magnesium sulfate and evaporation of the solvent gave the product as an oil. Yield 1.05 g, 65%. the product was extracted with two portions of ethyiacetate Drying over magnesium sulfate and evaporation of the solvent

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

Procedure: A solution of 5-chloro-2-methoxy benzeneboronic acid (1.9 g, 10 mmol) in hydrogen peroxide (2.04 ml, 30% solution) and ethanol 40 ml was refluxed for 30 min. Water was added and the product was extracted with two portions of ethyiacetate. Drying over magnesium sulfate and evaporation of the solvent gave the product as an oil. Yield 1.05 g, 65%. the product was extracted with two portions of ethyiacetate Drying over magnesium sulfate and evaporation of the solvent

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

Procedure: A solution of 2-bromo-4-chloroanisole (5.0 g, 22.6 mmol) in dry THF (60 ml) under nitrogen was cooled to −70° C. and n-butyl lithium (12.4 ml of a 2.0 M solution in hexanes, 24.8 mmol) was added. After 10 min. at −70° C. trlbutyl borate (8.5 ml, 31.4 mmol) was added and the temperature was allowed to rise to room temperature overnight. Aqueous hydrochloric acid (40 ml, 2 M) was added and the product was extracted with 2×60 ml ether. The ethereal phase was extracted with aqueous sodium hydroxide (2×40 ml, 1 M). Acidification with concentrated HCl during ice-cooling gave a precipitate that was dissolved in ether. Drying over magnesium sulfate and evaporation of the solvent gave the title compound. Yield 1.93 g, 46%. the product was extracted with 2×60 ml ether The ethereal phase was extracted with aqueous sodium hydroxide (2×40 ml, 1 M) Acidification with concentrated HCl during ice-cooling gave a precipitate that Drying over magnesium sulfate and evaporation of the solvent