1-bromo-3-ethylbenzene

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:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 1-bromo-3-ethylbenzene (2.0 g, 10.8 mmol) in deoxygenated N,N-dimethylformamide (50 ml) under nitrogen was added tributylvinyltin (5.0 g, 16.2 mmol) and tetrakistriphenylphosphine palladium (0) (500 mg, 4 mol %) and the reaction mixture was heated to 75° C. for 7 h. The cooled reaction mixture was poured onto water (400 ml) and extracted with diethyl ether (5×200 ml). The combined extracts were dried (MgSO4), filtered and concentrated in vacuo to afford the crude product. This was distilled under reduced pressure to afford a residue that was partitioned between water and hexane. The layers were separated and the aqueous layer was extracted with hexane. The combined extracts were dried (MgSO4), filtered and concentrated in vacuo to afford the title compound as a colourless oil (1.4 g, 98%). The cooled reaction mixture was poured onto water (400 ml) extracted with diethyl ether (5×200 ml) The combined extracts were dried (MgSO4) filtered concentrated in vacuo to afford the crude product This was distilled under reduced pressure to afford a residue that was partitioned between water and hexane The layers were separated the aqueous layer was extracted with hexane The combined extracts were dried (MgSO4) filtered concentrated in vacuo

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

Procedure: n-Butyllithium (34 ml of a 2.5M solution in hexanes) was added to a solution of 1-bromo-3-ethylbenzene (15 g) in tetrahydrofuran (320 ml) at −78° C. After 1 hour N,N-dimethylformamide (15 ml) was added. The mixture was stirred at −78° C. for 1 hour and allowed to warm to room temperature. The mixture was quenched with aqueous ammonium chloride and partitioned between ethyl acetate and water. The organic phase was dried (MgSO4) and evaporated. The residue was dissolved in methanol (250 ml) and treated with sodium borohydride (1.51 g) portionwise. The mixture was stirred at room temperature for 16 hours, quenched with 2M HCl (100 ml) and stirred for 4 hours. The mixture was concentrated under reduced pressure and the residue partitioned between ethyl acetate and 2M HCl. The organic phase was dried (MgSO4), evaporated and the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane. to warm to room temperature The mixture was quenched with aqueous ammonium chloride partitioned between ethyl acetate and water The organic phase was dried (MgSO4) evaporated The residue was dissolved in methanol (250 ml) treated with sodium borohydride (1.51 g) portionwise The mixture was stirred at room temperature for 16 hours quenched with 2M HCl (100 ml) stirred for 4 hours The mixture was concentrated under reduced pressure the residue partitioned between ethyl acetate and 2M HCl The organic phase was dried (MgSO4) evaporated the residue purified by chromatography eluting with 5-10% ethyl acetate in isohexane

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

Procedure: A solution of 3-bromo-ethylbenzene (25 g) in dry tetrahydrofuran (350 ml) at −70° C. was treated dropwise with n-butyllithium (59 ml of a 2.5M solution in hexanes) and stirred for 1 hour. N,N-Dimethylformamide (30 ml) was added and the solution was stirred at −70° C. for 1 hour and allowed to warm to room temperature. The reaction mixture was partitioned between saturated ammonium chloride solution and ethyl acetate. The organic phase was washed with 1N hydrochloric acid, dried (MgSO4) and evaporated. the solution was stirred at −70° C. for 1 hour The reaction mixture was partitioned between saturated ammonium chloride solution and ethyl acetate The organic phase was washed with 1N hydrochloric acid dried (MgSO4) evaporated

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

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

Procedure: Argon was bubbled into a solution of 1-bromo-3-ethylbenzene (2.5 g, 13.5 mmol) in DMF (37 ml) for 10 min. and then zinc cyanide (1.75 g, 14.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.56 g, 1.35 mmol) were added. After stirring at 80° C. overnight the reaction mixture was diluted with ethyl acetate (35 ml) then filtered through celite to remove the precipitate. The filtrate was washed with water (3×), saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by flash column chromatography using 2% ethyl acetate in hexane affording a colorless liquid (1.42 g). GC-MS (M+): 131.18. then filtered through celite to remove the precipitate The filtrate was washed with water (3×), saturated brine dried over anhydrous sodium sulfate filtered concentrated The product was purified by flash column chromatography

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

Procedure: Argon was bubbled into a solution of 1-bromo-3-ethylbenzene (2.5 g, 13.5 mmol) in DMF (37 ml) for 10 min. and then zinc cyanide (1.75 g, 14.9 mmol) and tetrakis(triphenylphosphine)palladium(0) (1.56 g, 1.35 mmol) were added. After stirring at 80° C. overnight the reaction mixture was diluted with ethyl acetate (35 ml) then filtered through celite to remove the precipitate. The filtrate was washed with water (3×), saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated. The product was purified by flash column chromatography using 2% ethyl acetate in hexane affording a colorless liquid (1.42 g). GC-MS (M+): 131.18. then filtered through celite to remove the precipitate The filtrate was washed with water (3×), saturated brine dried over anhydrous sodium sulfate filtered concentrated The product was purified by flash column chromatography

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

Procedure: A mixture of 1-bromo-3-ethylbenzene (9.79 g), cesium carbonate (45.0 g), 2-(2-propynyloxy)tetrahydropyran (11.2 ml), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (1.51 g), bis(acetonitrile)palladium(II) dichloride (274 mg) and acetonitrile (300 ml) was stirred at 90° C. for 10 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate, washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-95:5) to give the object product (5.25 g) as a yellow oil. the mixture was extracted with ethyl acetate washed with saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure The residue was purified by silica gel column chromatography (hexane:ethyl acetate=99:1-95:5)

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

Procedure: A solution (45 mL) of 1-bromo-3-ethylbenzene (5.1 g, 28 mmol) in tetrahydrofuran was added dropwise to a mixture (5.0 mL) of magnesium turnings (0.74 g, 31 mmol) and tetrahydrofuran under an argon atmosphere, and the mixture was stirred as it was for 30 min. The reaction mixture was added to the crushed dry ice and the mixture was stirred as it was for 1 h. 1N Hydrochloric acid was added to the reaction mixture and the mixture was extracted with ethyl acetate. The extract was dried, filtrated and concentrated. The residue was purified by silica gel column chromatography (hexane-ethyl acetate=5:1) to give the title compound (3.87 g, yield 93%). oil. the mixture was stirred as it was for 1 h the mixture was extracted with ethyl acetate The extract was dried filtrated concentrated The residue was purified by silica gel column chromatography (hexane-ethyl acetate=5:1)