1-bromo-3-(methoxymethyl)benzene

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

Procedure: To a solution of 3-bromobenzyl bromide (15.0 g, 60 mmol) in methanol-dimethoxyethane (DME) (30 ml+10 ml), sodium methylate (4.9 g, 90 mmol) was added under cooling with ice. The mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into water and extracted with ether. The organic layer was washed by an aqueous saturated solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off to obtain the title compound ( 12.1 g) having the following physical data. under cooling with ice extracted with ether The organic layer was washed by an aqueous saturated solution of sodium chloride dried over magnesium sulfate The solvent was distilled off

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

Procedure: A solution of lithium diisopropylamide (LDA, 2.0 M in heptane/THF, ethyl benzene, 42.2 mL, 84.4 mmol) was added drop-wise to a solution of ethyl isobutyrate (9.78 g, 84.3 mmol) in anhydrous THF (30 mL) at −78° C. The mixture was allowed to stir at −78° C. for 1 h, before 3,3′-bis(bromomethyl)benzophenone ((prepared according to Shultz, D. A.; Fox, M. A. J. Am. Chem. Soc. 1989, 16, 6311, from 3-bromobenzyl methyl ether (Friedman, L.; Shechter, H. J. Org. Chem. 1961, 26, 2522), 10.34 g, 28.1 mmol) was added, followed by addition of DMPU (2.7 g, 17 mmol). The mixture was stirred for 30 min at −78° C., allowed to warm to rt, and stirred for 30 min. The THF was removed under reduced pressure and the residue was diluted with saturated NH4Cl (280 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL), then dried over anhydrous Na2SO4 and concentrated in vacuo to furnish 3-{3-[3-(2-ethoxycarbonyl-2-methyl-propyl)-benzoyl]-phenyl}-2,2-dimethyl -prop ionic acid ethyl ester (11.0 g, 90%) as an oil. 1H NMR (300 MHz, CDCl3): δ (ppm): 7.8-7.2 (m, 8H), 3.98 (q, J=6.9 Hz, 4H), 2.83 (s, 4H), 1.2-0.8 (m, 18H). 13C NMR (75 MHz, CDCl3): δ (ppm): 196.5, 176.8, 138.1, 137.2, 134.0, 131.4, 128.1, 127.7, 60.3, 45.7, 43.3, 24.8, 13.9. prepared to warm to rt stirred for 30 min The THF was removed under reduced pressure the residue was diluted with saturated NH4Cl (280 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL) dried over anhydrous Na2SO4 concentrated in vacuo

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

Procedure: A solution of lithium diisopropylamide (LDA, 2.0 M in heptane/THF, ethyl benzene, 42.2 mL, 84.4 mmol) was added drop-wise to a solution of ethyl isobutyrate (9.78 g, 84.3 mmol) in anhydrous THF (30 mL) at −78° C. The mixture was allowed to stir at −78° C. for 1 h, before 3,3′-bis(bromomethyl)benzophenone ((prepared according to Shultz, D. A.; Fox, M. A. J. Am. Chem. Soc. 1989, 16, 6311, from 3-bromobenzyl methyl ether (Friedman, L.; Shechter, H. J. Org. Chem. 1961, 26, 2522), 10.34 g, 28.1 mmol) was added, followed by addition of DMPU (2.7 g, 17 mmol). The mixture was stirred for 30 min at −78° C., allowed to warm to rt, and stirred for 30 min. The THF was removed under reduced pressure and the residue was diluted with saturated NH4Cl (280 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL), then dried over anhydrous Na2SO4 and concentrated in vacuo to furnish 3-{3-[3-(2-ethoxycarbonyl-2-methyl-propyl)-benzoyl]-phenyl}-2,2-dimethyl -prop ionic acid ethyl ester (11.0 g, 90%) as an oil. 1H NMR (300 MHz, CDCl3): δ (ppm): 7.8-7.2 (m, 8H), 3.98 (q, J=6.9 Hz, 4H), 2.83 (s, 4H), 1.2-0.8 (m, 18H). 13C NMR (75 MHz, CDCl3): δ (ppm): 196.5, 176.8, 138.1, 137.2, 134.0, 131.4, 128.1, 127.7, 60.3, 45.7, 43.3, 24.8, 13.9. prepared to warm to rt stirred for 30 min The THF was removed under reduced pressure the residue was diluted with saturated NH4Cl (280 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL) dried over anhydrous Na2SO4 concentrated in vacuo

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

Procedure: To a solution of 3-bromobenzylbromide (15.0 g) in methanol-dimethoxyethane (30 ml+10 ml) was added sodium methylate (4.9 g) under cooling with ice and the mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into water. The reaction mixture was extracted with ether. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and the solvent was evaporated to give the title compound (12.1 g) having the following physical data. under cooling with ice The reaction mixture was extracted with ether The organic layer was washed with a saturated aqueous solution of sodium chloride dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: To a solution of 3-bromobenzyl bromide (15.0 g, 60 mmol) in methanol-dimethoxyethane (DME) (30 ml+10 ml), sodium methylate (4.9 g, 90 mmol) was added under cooling with ice. The mixture was stirred for 1 hour at room temperature. The reaction mixture was poured into water and extracted with ether. The organic layer was washed by an aqueous saturated solution of sodium chloride and dried over magnesium sulfate. The solvent was distilled off to obtain the title compound ( 12.1 g) having the following physical data. under cooling with ice extracted with ether The organic layer was washed by an aqueous saturated solution of sodium chloride dried over magnesium sulfate The solvent was distilled off

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

Procedure: A solution of lithium diisopropylamide (LDA, 2.0 M in heptane/THF, ethyl benzene, 42.2 mL, 84.4 mmol) was added drop-wise to a solution of ethyl isobutyrate (9.78 g, 84.3 mmol) in anhydrous THF (30 mL) at −78° C. The mixture was allowed to stir at −78° C. for 1 h, before 3,3′-bis(bromomethyl)benzophenone ((prepared according to Shultz, D. A.; Fox, M. A. J. Am. Chem. Soc. 1989, 16, 6311, from 3-bromobenzyl methyl ether (Friedman, L.; Shechter, H. J. Org. Chem. 1961, 26, 2522), 10.34 g, 28.1 mmol) was added, followed by addition of DMPU (2.7 g, 17 mmol). The mixture was stirred for 30 min at −78° C., allowed to warm to rt, and stirred for 30 min. The THF was removed under reduced pressure and the residue was diluted with saturated NH4Cl (280 mL). The aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL), then dried over anhydrous Na2SO4 and concentrated in vacuo to furnish 3-{3-[3-(2-ethoxycarbonyl-2-methyl-propyl)-benzoyl]-phenyl}-2,2-dimethyl -prop ionic acid ethyl ester (11.0 g, 90%) as an oil. 1H NMR (300 MHz, CDCl3): δ (ppm): 7.8-7.2 (m, 8H), 3.98 (q, J=6.9 Hz, 4H), 2.83 (s, 4H), 1.2-0.8 (m, 18H). 13C NMR (75 MHz, CDCl3): δ (ppm): 196.5, 176.8, 138.1, 137.2, 134.0, 131.4, 128.1, 127.7, 60.3, 45.7, 43.3, 24.8, 13.9. prepared to warm to rt stirred for 30 min The THF was removed under reduced pressure the residue was diluted with saturated NH4Cl (280 mL) The aqueous layer was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine (200 mL), 5% HCl (100 mL), and saturated NaHCO3 solution (50 mL) dried over anhydrous Na2SO4 concentrated in vacuo