(5-bromo-2-methoxyphenyl)methanol

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: To a solution of (5-bromo-2-methoxyphenyl)methanol (1.0 g, 4.6 mmol) in dichloromethane (10 mL) at 0° C. was added tribromophosphine (1 M in dichloromethane, 9.2 mL, 9.2 mmol). The ice bath was removed and the reaction stirred for 15 min. The reaction was concentrated, poured onto cold saturated sodium bicarbonate, extracted with pentane, dried over magnesium sulfate, and concentrated to give 1.15 g (89%) as a white crystalline solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.44 (d, J=2.5 Hz, 1H), 7.38 (dd, J=8.9, 6.1 Hz, 1H), 4.47 (s, 2H), 3.87 (s, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 156.7, 133.6, 132.8, 128.4, 112.8, 112.7, 56.0, 27.5. The ice bath was removed The reaction was concentrated poured onto cold saturated sodium bicarbonate extracted with pentane dried over magnesium sulfate concentrated to give 1.15 g (89%) as a white crystalline solid

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

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

Procedure: To a solution of (5-bromo-2-methoxyphenyl)methanol (1.0 g, 4.6 mmol) in dichloromethane (10 mL) at 0° C. was added tribromophosphine (1 M in dichloromethane, 9.2 mL, 9.2 mmol). The ice bath was removed and the reaction stirred for 15 min. The reaction was concentrated, poured onto cold saturated sodium bicarbonate, extracted with pentane, dried over magnesium sulfate, and concentrated to give 1.15 g (89%) as a white crystalline solid. 1H NMR (500 MHz, CDCl3) δ ppm 7.44 (d, J=2.5 Hz, 1H), 7.38 (dd, J=8.9, 6.1 Hz, 1H), 4.47 (s, 2H), 3.87 (s, 3H); 13C NMR (126 MHz, CDCl3) δ ppm 156.7, 133.6, 132.8, 128.4, 112.8, 112.7, 56.0, 27.5. The ice bath was removed The reaction was concentrated poured onto cold saturated sodium bicarbonate extracted with pentane dried over magnesium sulfate concentrated to give 1.15 g (89%) as a white crystalline solid

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: To a solution of 5-bromo-2-methoxybenzyl alcohol (1.0 g, 4.6 mmol) and imidazole (470 mg, 7.01 mmol) in DMF (15 ml) was added tert-butyldimethylsilyl chloride (1.04 g, 6.91 mmol). The mixture was allowed to stir for 4 h, poured onto water (100 ml) and extracted with ether (3×30 ml). The combined organic phases were washed with water (50 ml), brine (50 ml), dried over sodium sulfate and evaporated under reduced pressure to leave a pale yellow oil. This was purified by chromatography (SiO2, 5% ether/petrol), to give the title compound (1.46 g, 96%) as a colourless oil. poured onto water (100 ml) extracted with ether (3×30 ml) The combined organic phases were washed with water (50 ml), brine (50 ml) dried over sodium sulfate evaporated under reduced pressure to leave a pale yellow oil This was purified by chromatography (SiO2, 5% ether/petrol)

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

Procedure: 0.8 g of 5-bromo-2-methoxyphenyl methanol was dissolved in 30 ml tetrahydrofuran. 2.6 g of 4-(trifluoromethyl)benzyl bromide and 0.22 g of sodium hydride (60% oily) were added thereto, followed by stirring at room temperature for 16 hours. Water was added to the reaction solution, followed by extracting with diethyl ether. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was subjected to silica gel column chromatography, to give 1.4 g of 4-bromo-1-methoxy-2-({[4-(trifluoromethyl)benzyl]oxy}methyl)benzene from fractions eluted with hexane-ethyl acetate (9:1). by extracting with diethyl ether The organic layer was washed with brine dried over anhydrous magnesium sulfate the solvent was evaporated

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

Procedure: 3-(2-Oxo-2,3-dihydro-benzoimidazol-1-yl)-hexanoic acid ethyl ester (96.7 mg, 0.35 mmol), prepared as described above, (5-bromo-2-methoxy-phenyl)-methanol (152 mg, 0.7 mmol) and triphenylphosphene (183.6, 0.7 mmol) were combined in a reaction vial and THF (1 mL) was added. The mixture was stirred until complete solution was attained, then cooled to 0° C., and diisopropylazodicarboxylate (0.136 mL, 0.7 mmol) was added dropwise. The reaction mixture was agitated at room temperature overnight, diluted with THF (2 mL) then treated directly with the Amberlyst® resin (3 g, 4 mmol). This reaction mixture was agitated overnight and the resin was then filtered and washed with DMF (2×3 mL) and several portions of methanol. The product was eluted by treating the resin with a 20% solution of formic acid in methanol (5 mL) and washing with methanol (3 mL). The combined eluant and final wash was evaporated to provide the title compound (154 mg, 99%). LCMS (ESMS): m/z 447/9 (M+H+). was added The reaction mixture was agitated at room temperature overnight This reaction mixture was agitated overnight the resin was then filtered washed with DMF (2×3 mL) and several portions of methanol The product was eluted by treating the resin with a 20% solution of formic acid in methanol (5 mL) washing with methanol (3 mL) The combined eluant and final wash was evaporated

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

Procedure: Imidazole (3.45 g) and t-butyldimethylchlorosilane (17.6 g) were added to a solution of 5-bromo-2-methoxybenzyl alcohol (10.0 g) in DMF (100 ml) under cooling with ice and the mixture was stirred for two hours. The reaction mixture was added to ice-cooled water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain [(5-bromo-2-methoxybenzyl)oxy](t-butyl)dimethylsilane (15.2 g). under cooling with ice The reaction mixture was added to ice- extracted with ethyl acetate The organic layer was washed with saturated brine dried over anhydrous sodium sulfate After filtration the filtrate was concentrated The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate)