2-bromo-6-chlorobenzaldehyde

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

Procedure: 2-Chloro-6-bromobenzaldehyde (200 mg, 0.91 mmol), pyridine-4-boronic acid (125 mg, 1.0 mmol), dichlorobis(triphenylphosphine)palladium (II) (5 mol %, 30 mg), acetonitrile (2 mL) and aqueous sodium carbonate (2 molar solution, 2 mL) were combined in a microwave vial and sealed with a crimp seal. The mixture was microwaved at 150° C. for 5 min. The crude reaction mixture was then poured over Celite and washed with acetonitrile. The mixture was concentrated under reduced pressure and taken up in ethyl acetate. This organic solution was successively washed with water and brine, then dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 98:2 methylene chloride:methanol to provide 2-chloro-6-(4-pyridyl)benzaldehyde (100 mg, 51% yield). NMR (300 MHz, CDCl3): 10.3 (s, 1H), 8.65 (m, 2H), 7.55 (m, 2H), 7.2 ppm (m, 3H). sealed with a crimp seal The mixture was microwaved at 150° C. for 5 min The crude reaction mixture was then poured over Celite washed with acetonitrile The mixture was concentrated under reduced pressure This organic solution was successively washed with water and brine dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The resulting residue was purified by flash column chromatography on silica gel eluting with 98:2 methylene chloride

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.6 molar solution of butyllithium in hexanes (4.5 mL, 2.8 mmol) was placed in a three-neck flask equipped with a stirrer, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0° C. A solution of diisopropyl amine (1.13 mL, 8.1 mmol) in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0° C. for ten minutes, then cooled to −78° C. Upon cooling, a solution of 1-bromo-3-chlorobenzene (1.4 g, 7.3 mmol) in anhydrous tetrahydrofuran was added dropwise. The reaction was allowed to stir at −78° C. for one hour. Anhydrous dimethylformamide (636 μL) was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid (50 mL) and water (50 mL). The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with 9:1 hexanes:ethyl acetate to yield 2-chloro-6-bromobenzaldehyde as an off white solid (850 mg, 53% yield). NMR (300 MHz, CDCl3): 10.4 (s, 1H), 7.6 (m, 1H), 7.45 (m, 1H), 7.3 ppm (m, 1H). equipped with a stirrer, addition funnel at 0° C cooled to −78° C Upon cooling to stir at −78° C. for one hour to slowly warm to room temperature The aqueous mixture was extracted with ether twice the ether layers were separated The combined ether layers were successively washed with aqueous hydrochloric acid and brine The separated organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The resulting residue was purified by flash column chromatography on silica gel eluting with 9:1 hexanes

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 1.6 molar solution of butyllithium in hexanes was placed in a three-neck flask equipped with a stirrer, addition funnel, low-temperature thermometer and nitrogen inlet tube at 0° C. A solution of diisopropyl amine in anhydrous tetrahydrofuran was added dropwise. The resulting solution was stirred at 0° C. for ten minutes, then cooled to −78° C. Upon cooling, a solution of 1-bromo-3-chlorobenzene in anhydrous tetrahydrofuran was added dropwise. The reaction was stirred at −78° C. for one hour. Anhydrous dimethylformamide was added. The solution was allowed to slowly warm to room temperature, followed by the addition of acetic acid and water. The aqueous mixture was extracted with ether twice and the ether layers were separated. The combined ether layers were successively washed with aqueous hydrochloric acid and brine. The separated organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography on silica gel, eluting with hexanes-ethyl acetate to yield 2-chloro-6-bromobenzaldehyde. equipped with a stirrer, addition funnel at 0° C cooled to −78° C Upon cooling The reaction was stirred at −78° C. for one hour to slowly warm to room temperature The aqueous mixture was extracted with ether twice the ether layers were separated The combined ether layers were successively washed with aqueous hydrochloric acid and brine The separated organic layer was dried over anhydrous sodium sulfate filtered concentrated under reduced pressure The resulting residue was purified by flash column chromatography on silica gel eluting with hexanes-ethyl acetate