1-bromo-4-[2-(2-methoxyethoxy)ethoxy]benzene

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

Procedure: Magnesium turnings (0.83g, 0.032 mol) and 10 mL of anhydrous tetrahydrofuran (THF) were placed in a dry 3-necked round bottom flask. The mixture was stirred under reflux in an argon atmosphere for about 20 minutes. The previously prepared 4-[2-(2-methoxyethoxy)ethoxy]bromobenzene (7-Og, 0.025 mol) in 30 mL of anhydrous THF was slowly dripped into the stirring magnesium mixture. A small amount (about 0.1 mL) of 1,2-dibromoethane was initially added to start the Grignard reaction. After the bromide was added, the mixture was refluxed overnight under an argon atmosphere. The mixture was then cooled to -78° C. and 15 mL (0.17 mol) of allyl bromide in 30 mL of spectral grade benzene was added. The resulting mixture was stirred and allowed to slowly warm to room temperature and then refluxed overnight. The mixture was cooled and exacted with ethyl ether. The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine and then with water until the organic layer was neutral. The ethyl ether solution was dried over anhydrous magnesium sulfate and the solvent was removed. The product was distilled to give 2.78 g (47%) of the desired 3-(4-[2-(2-methoxyethoxy) ethoxy]phenyl]-1-propene, bp 105°-113° C./0.2mm; NMR(δ): 3.30(2H,d), 3.36(3H,s), 3.46-3.92(6H,m), 4.12(2H,m), 5.00(2H,m), 5.95(1H,m), 6.80(2H,d), 7.04(2H,d). under reflux in an argon atmosphere for about 20 minutes the Grignard reaction the mixture was refluxed overnight under an argon atmosphere The resulting mixture was stirred to slowly warm to room temperature refluxed overnight The mixture was cooled The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine The ethyl ether solution was dried over anhydrous magnesium sulfate the solvent was removed The product was distilled

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

Procedure: Magnesium turnings (0.83g, 0.032 mol) and 10 mL of anhydrous tetrahydrofuran (THF) were placed in a dry 3-necked round bottom flask. The mixture was stirred under reflux in an argon atmosphere for about 20 minutes. The previously prepared 4-[2-(2-methoxyethoxy)ethoxy]bromobenzene (7-Og, 0.025 mol) in 30 mL of anhydrous THF was slowly dripped into the stirring magnesium mixture. A small amount (about 0.1 mL) of 1,2-dibromoethane was initially added to start the Grignard reaction. After the bromide was added, the mixture was refluxed overnight under an argon atmosphere. The mixture was then cooled to -78° C. and 15 mL (0.17 mol) of allyl bromide in 30 mL of spectral grade benzene was added. The resulting mixture was stirred and allowed to slowly warm to room temperature and then refluxed overnight. The mixture was cooled and exacted with ethyl ether. The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine and then with water until the organic layer was neutral. The ethyl ether solution was dried over anhydrous magnesium sulfate and the solvent was removed. The product was distilled to give 2.78 g (47%) of the desired 3-(4-[2-(2-methoxyethoxy) ethoxy]phenyl]-1-propene, bp 105°-113° C./0.2mm; NMR(δ): 3.30(2H,d), 3.36(3H,s), 3.46-3.92(6H,m), 4.12(2H,m), 5.00(2H,m), 5.95(1H,m), 6.80(2H,d), 7.04(2H,d). under reflux in an argon atmosphere for about 20 minutes the Grignard reaction the mixture was refluxed overnight under an argon atmosphere The resulting mixture was stirred to slowly warm to room temperature refluxed overnight The mixture was cooled The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine The ethyl ether solution was dried over anhydrous magnesium sulfate the solvent was removed The product was distilled

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

Procedure: To a cooled (0° C.) suspension of dry NaH (0.512 g, 21.4 mmol) in anhydrous DMF (10 mL) under an Argon atmosphere, a solution of 4-bromophenol (3.11 g, 17.8 mmol) in anhydrous DMF (20 mL) was added dropwise over 2-3 min. The mixture was stirred at 0° C. for 10 min and then allowed to warm to rt over 30 min. To the resulting white suspension was added 1-bromo-2-(2-methoxyethoxy)ethane (2.66 mL, 19.6 mmol) dropwise over 2 min and the mixture was stirred at rt for 30 min and then at 65° C. for 1.5 h. After cooling to rt, the mixture was concentrated under reduced pressure to an oily suspension, diluted with brine (80 mL), and the mixture was extracted with EtOAc (3×60 mL). The combined extracts were washed with brine (2×25 mL), dried over Na2SO4, filtered, and concentrated to give compound 85a as a mobile, pale amber-colored oil, used in the following reaction without further purification. Mass spectrum (LCMS, ESI pos.): Calcd. for C11H15BrO3, 275.0/277.0 (M+H). found 275.2/277.1 To a cooled to warm to rt over 30 min the mixture was stirred at rt for 30 min at 65° C. for 1.5 h After cooling to rt the mixture was concentrated under reduced pressure to an oily suspension diluted with brine (80 mL) the mixture was extracted with EtOAc (3×60 mL) The combined extracts were washed with brine (2×25 mL) dried over Na2SO4 filtered concentrated

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

Procedure: Magnesium turnings (0.83g, 0.032 mol) and 10 mL of anhydrous tetrahydrofuran (THF) were placed in a dry 3-necked round bottom flask. The mixture was stirred under reflux in an argon atmosphere for about 20 minutes. The previously prepared 4-[2-(2-methoxyethoxy)ethoxy]bromobenzene (7-Og, 0.025 mol) in 30 mL of anhydrous THF was slowly dripped into the stirring magnesium mixture. A small amount (about 0.1 mL) of 1,2-dibromoethane was initially added to start the Grignard reaction. After the bromide was added, the mixture was refluxed overnight under an argon atmosphere. The mixture was then cooled to -78° C. and 15 mL (0.17 mol) of allyl bromide in 30 mL of spectral grade benzene was added. The resulting mixture was stirred and allowed to slowly warm to room temperature and then refluxed overnight. The mixture was cooled and exacted with ethyl ether. The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine and then with water until the organic layer was neutral. The ethyl ether solution was dried over anhydrous magnesium sulfate and the solvent was removed. The product was distilled to give 2.78 g (47%) of the desired 3-(4-[2-(2-methoxyethoxy) ethoxy]phenyl]-1-propene, bp 105°-113° C./0.2mm; NMR(δ): 3.30(2H,d), 3.36(3H,s), 3.46-3.92(6H,m), 4.12(2H,m), 5.00(2H,m), 5.95(1H,m), 6.80(2H,d), 7.04(2H,d). under reflux in an argon atmosphere for about 20 minutes the Grignard reaction the mixture was refluxed overnight under an argon atmosphere The resulting mixture was stirred to slowly warm to room temperature refluxed overnight The mixture was cooled The ethyl ether layer was washed with aqueous 3N hydrochloric acid, aqueous saturated brine The ethyl ether solution was dried over anhydrous magnesium sulfate the solvent was removed The product was distilled