2-[2-[2-[2-[2-[2-(BENZYLOXY)ETHOXY]ETHOXY]ETHOXY]ETHOXY]ETHOXY]ETHANOL

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

Procedure: Triethylamine (1.45 mL, 10.74 mmol) and methanesulfonyl chloride (0.48 mL, 5.9 mmol) were added to a solution of hexaethyleneglycol monobenzyl ether (2.0 g, 5.37 mmol) in methylene chloride (30 mL) at 0° C. and the solution was stirred for 30 min at ice bath temperature. The reaction mixture was filtered and concentrated to an oil which was dissolved in 30% ammonium hydroxide solution (50 mL). The reaction mixture was heated at reflux for 3 days and concentrated. Residual water was removed by evaporation from toluene and the crude material was slurried with THF and filtered. The filtrate was concentrated at reduced pressure to provide the title compound as an amber oil (1.14 g, 57% yield). 1H-NMR (300 MHz, DMSO-d6) δ: 7.77 (br s, 2H), 7.40-7.10 (m, 5H), 4.48 (s, 2H), 3.61-3.48 (m, 24H). The reaction mixture was filtered concentrated to an oil which was dissolved in 30% ammonium hydroxide solution (50 mL) The reaction mixture was heated at reflux for 3 days concentrated Residual water was removed by evaporation from toluene filtered The filtrate was concentrated at reduced pressure

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

Procedure: A solution of hexaethylene glycol monobenzyl ether from above (22.3 g) in anhydrous THF (100 ml) was added to a suspension of 50% NaH (3.5 g) in anhydrous THF (100 ml). The suspension was stirred at ambient temperature for 30 min and then a solution of triethylene glycol methyl tosyl ether from above (22.0 g) in THF (100 ml) was added dropwise. The mixture was refluxed under nitrogen overnight, cooled to ambient temperature, quenched with water (500 ml), and extracted with diethyl ether (3×300 ml). The ether extracts were combined, dried (sodium sulfate), and concentrated in vacuo to give nonaethylene glycol benzyl methyl ether as an oil (27 g, 88%), 1H-NMR (CDCl3) δ: 7.31 (m, 5, 5 phenyl CH), 4.54 (s, 2, benzyl CH2), 3.62-3.52 (m, 36, 18 CH2O), 3.35 (s, 3, CH3). The mixture was refluxed under nitrogen overnight cooled to ambient temperature quenched with water (500 ml) extracted with diethyl ether (3×300 ml) dried (sodium sulfate) concentrated in vacuo

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

Procedure: A solution of hexaethylene glycol monobenzyl ether from above (22.3 g) in anhydrous THF (100 ml) was added to a suspension of 50% NaH (3.5 g) in anhydrous THF (100 ml). The suspension was stirred at ambient temperature for 30 min and then a solution of triethylene glycol methyl tosyl ether from above (22.0 g) in THF (100 ml) was added dropwise. The mixture was refluxed under nitrogen overnight, cooled to ambient temperature, quenched with water (500 ml), and extracted with diethyl ether (3×300 ml). The ether extracts were combined, dried (sodium sulfate), and concentrated in vacuo to give nonaethylene glycol benzyl methyl ether as an oil (27 g, 88%), 1H-NMR (CDCl3) δ: 7.31 (m, 5, 5 phenyl CH), 4.54 (s, 2, benzyl CH2), 3.62-3.52 (m, 36, 18 CH2O), 3.35 (s, 3, CH3). The mixture was refluxed under nitrogen overnight cooled to ambient temperature quenched with water (500 ml) extracted with diethyl ether (3×300 ml) dried (sodium sulfate) concentrated in vacuo

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of hexaethylene glycol (Aldrich, 100 g) and benzyl bromide (Aldrich, 12 g) in aqueous sodium hydroxide (50% (w/w), 80 ml) was stirred at 100° C. (oil bath) under nitrogen for 2 h. The reaction mixture was then cooled to ambient temperature, diluted with water to a total volume of 500 ml, and extracted with diethyl ether (200 ml) to remove dibenzylated product. Sodium chloride (100 g) was added to the aqueous layer, which was extracted further with diethyl ether (6×100 ml). These ether extracts were combined, dried (sodium sulfate), and concentrated to give hexaethylene glycol monobenzyl ether as an oil (25 g, 20% based on glycol), 1H-NMR (CDCl3) δ: 7.30 (m, 5, 5 phenyl CH), 4.53 (s, 2, benzyl CH2), 3.69-3.54 (m, 22, 11 OCH2), 3.06 (br s, 3, OH and CH2O). The reaction mixture was then cooled to ambient temperature extracted with diethyl ether (200 ml) to remove dibenzylated product Sodium chloride (100 g) was added to the aqueous layer, which was extracted further with diethyl ether (6×100 ml) dried (sodium sulfate) concentrated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of hexaethylene glycol (Aldrich, 100 g) and benzyl bromide (Aldrich, 12 g) in aqueous sodium hydroxide (50% (w/w), 80 ml) was stirred at 100° C. (oil bath) under nitrogen for 2 h. The reaction mixture was then cooled to ambient temperature, diluted with water to a total volume of 500 ml, and extracted with diethyl ether (200 ml) to remove dibenzylated product. Sodium chloride (100 g) was added to the aqueous layer, which was extracted further with diethyl ether (6×100 ml). These ether extracts were combined, dried (sodium sulfate), and concentrated to give hexaethylene glycol monobenzyl ether as an oil (25 g, 20% based on glycol), 1H-NMR (CDCl3) δ: 7.30 (m, 5, 5 phenyl CH), 4.53 (s, 2, benzyl CH2), 3.69-3.54 (m, 22, 11 OCH2), 3.06 (br s, 3, OH and CH2O). The reaction mixture was then cooled to ambient temperature extracted with diethyl ether (200 ml) to remove dibenzylated product Sodium chloride (100 g) was added to the aqueous layer, which was extracted further with diethyl ether (6×100 ml) dried (sodium sulfate) concentrated

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An aqueous sodium hydroxide solution prepared by dissolving 3.99 g (100 mmol) NaOH in 4 ml water was added slowly to monodispersed hexaethylene glycol (28.175 g, 25 ml, 100 mmol). Benzyl chloride (3.9 g, 30.8 mmol, 3.54 ml) was added and the reaction mixture was heated with stirring to 100° C. for 18 hours. The reaction mixture was then cooled, diluted with brine (250 ml) and extracted with methylene chloride (200 ml×2). The combined organic layers were washed with brine once, dried over Na2SO4, filtered and concentrated in vacuo to a dark brown oil. The crude product mixture was purified via flash chromatography (silica gel, gradient elution: ethyl acetate to 9/1 ethyl acetate/methanol) to yield 8.099 g (70%) of monodispersed compound 1 as a yellow oil. the reaction mixture was heated The reaction mixture was then cooled extracted with methylene chloride (200 ml×2) The combined organic layers were washed with brine once dried over Na2SO4 filtered concentrated in vacuo to a dark brown oil The crude product mixture was purified via flash chromatography (silica gel, gradient elution: ethyl acetate to 9/1 ethyl acetate/methanol)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: An aqueous sodium hydroxide solution prepared by dissolving 3.99 g (100 mmol) NaOH in 4 ml water was added slowly to monodispersed hexaethylene glycol (28.175 g, 25 ml, 100 mmol). Benzyl chloride (3.9 g, 30.8 mmol, 3.54 ml) was added and the reaction mixture was heated with stirring to 100° C. for 18 hours. The reaction mixture was then cooled, diluted with brine (250 ml) and extracted with methylene chloride (200 ml×2). The combined organic layers were washed with brine once, dried over Na2SO4, filtered and concentrated in vacuo to a dark brown oil. The crude product mixture was purified via flash chromatography (silica gel, gradient elution: ethyl acetate to 9/1 ethyl acetate/methanol) to yield 8.099 g (70%) of monodispersed compound 1 as a yellow oil. the reaction mixture was heated The reaction mixture was then cooled extracted with methylene chloride (200 ml×2) The combined organic layers were washed with brine once dried over Na2SO4 filtered concentrated in vacuo to a dark brown oil The crude product mixture was purified via flash chromatography (silica gel, gradient elution: ethyl acetate to 9/1 ethyl acetate/methanol)

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of the product of step (a) (1 g) in dichloromethane (20 ml), p-toluenesulfonyl chloride (0.66 g) and triethylamine (0.5 ml) were added and the reaction was stirred at 20° C. for 24 hours. The reaction mixture was diluted with dichloromethane (100 ml) and washed with water (100 ml), brine (100 ml), dried and the solvent removed in vacuo. Purification by column chromatography on silica gel (Biotage) eluting with 10% ethyl acetate in cyclohexane gave the title compound (1 g). washed with water (100 ml), brine (100 ml) dried the solvent removed in vacuo Purification by column chromatography on silica gel (Biotage) eluting with 10% ethyl acetate in cyclohexane