2-[2-[2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethanol

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

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

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

Procedure: A solution of 73.91 g of p-toluenesulfonyl chloride (0.389 mol) in 400 mL of methylene chloride is added dropwise with stirring over a 2.5 hrs period to 400 niL of methylene chloride containing 50 g of hexaethylene glycol (0.177 mol) and 64 miL of triethylamine (39.36 g, 0.389 mol) at 0° C. The mixture is stirred for one hr at 0° C. and heated to ambient temperature for 44 hrs. The mixture is filtered and the filtrate concentrated in vacuo. The resulting residue is suspended in 500 mL of ethyl acetate and filtered. The filtrate is concentrated in vacuo to a yellow oil which was triturated eight times with 250 mL portions of warm hexane to remove unreacted p-toluenesulfonyl chloride. The resulting oil is then concentrated under high vacuum to yield 108.12 g of a yellow oil (quantitative yield). heated to ambient temperature for 44 hrs The mixture is filtered the filtrate concentrated in vacuo filtered The filtrate is concentrated in vacuo to a yellow oil which was triturated eight times with 250 mL portions of warm hexane to remove unreacted p-toluenesulfonyl chloride The resulting oil is then concentrated under high vacuum

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

Procedure: A solution of 73.91 g of p-toluenesulfonyl chloride (0.389 mol) in 400 mL of methylene chloride is added dropwise with stirring over a 2.5 hrs period to 400 niL of methylene chloride containing 50 g of hexaethylene glycol (0.177 mol) and 64 miL of triethylamine (39.36 g, 0.389 mol) at 0° C. The mixture is stirred for one hr at 0° C. and heated to ambient temperature for 44 hrs. The mixture is filtered and the filtrate concentrated in vacuo. The resulting residue is suspended in 500 mL of ethyl acetate and filtered. The filtrate is concentrated in vacuo to a yellow oil which was triturated eight times with 250 mL portions of warm hexane to remove unreacted p-toluenesulfonyl chloride. The resulting oil is then concentrated under high vacuum to yield 108.12 g of a yellow oil (quantitative yield). heated to ambient temperature for 44 hrs The mixture is filtered the filtrate concentrated in vacuo filtered The filtrate is concentrated in vacuo to a yellow oil which was triturated eight times with 250 mL portions of warm hexane to remove unreacted p-toluenesulfonyl chloride The resulting oil is then concentrated under high vacuum

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

Procedure: 25 g (88.5 mmol) of hexaethyleneglycol was stirred at 0° C. in 200 mL of CH2Cl2, and 14.3 mL of pyridine (177 mmol; 2 eq.) was added to the mixture followed by 17.4 g (88.5 mmol) of tosylchloride. The reaction mixture was stirred at room temperature for 24 hours and partitioned between 400 ml of 1N HCl and 200 ml of CH2Cl2. The organic layer was dried over MgSO4, filtered, and concentrated to provide 31 g of a light yellow oil. Purification by silica gel chromatography (CH2Cl2/MeOH) provided 15.32 g (40%) of 1 as a light yellow oil: 1H NMR (CDCl3) δ2.45 (s, 3H), 3.55-3.75 (m, 22H), 4.15 (t, 2H), 7.35 (d, 2H), 7.80 (d, 2H); HRMS (FAB) calculated for C19H33O9S (M+H): 437.1845. Found: 437.1834. partitioned between 400 ml of 1N HCl and 200 ml of CH2Cl2 The organic layer was dried over MgSO4 filtered concentrated

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

Procedure: Monodispersed activated hexaethylene glycol monomethyl ether was prepared analogously to that of monodispersed triethylene glycol in Example 6 above. A 20% phosgene in toluene solution (35 mL, 6.66 g, 67.4 mmol phosgene) was chilled under a N2 atmosphere in an ice/salt water bath. Monodispersed hexaethylene glycol (1.85 mL, 2.0 g, 6.74 mmol) was dissolved in 5 mL anhydrous EtOAc and added to the phosgene solution via syringe. The reaction mixture was kept stirring in the ice bath for one hour, removed and stirred a further 2.5 hours at room temperature. The phosgene, EtOAc, and toluene were removed by vacuum distillation, leaving monodispersed methyl hexaethylene glycol chloroformate as a clear, oily residue. removed The phosgene, EtOAc, and toluene were removed by vacuum distillation

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

Procedure: Monodispersed activated hexaethylene glycol monomethyl ether was prepared analogously to that of monodispersed triethylene glycol in Example 6 above. A 20% phosgene in toluene solution (35 mL, 6.66 g, 67.4 mmol phosgene) was chilled under a N2 atmosphere in an ice/salt water bath. Monodispersed hexaethylene glycol (1.85 mL, 2.0 g, 6.74 mmol) was dissolved in 5 mL anhydrous EtOAc and added to the phosgene solution via syringe. The reaction mixture was kept stirring in the ice bath for one hour, removed and stirred a further 2.5 hours at room temperature. The phosgene, EtOAc, and toluene were removed by vacuum distillation, leaving monodispersed methyl hexaethylene glycol chloroformate as a clear, oily residue. removed The phosgene, EtOAc, and toluene were removed by vacuum distillation

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

Procedure: Monodispersed activated hexaethylene glycol monomethyl ether was prepared analogously to that of monodispersed triethylene glycol as described herein. A 20% phosgene in toluene solution (35 mL, 6.66 g, 67.4 mmol phosgene) was chilled under a N2 atmosphere in an ice/salt water bath. Monodispersed hexaethylene glycol (1.85 mL, 2.0 g, 6.74 mmol) was dissolved in 5 mL anhydrous EtOAc and added to the phosgene solution via syringe. The reaction mixture was kept stirring in the ice bath for one hour, removed and stirred a further 2.5 hours at room temperature. The phosgene, EtOAc, and toluene were removed by vacuum distillation, leaving monodispersed methyl hexaethylene glycol chloroformate as a clear, oily residue. removed The phosgene, EtOAc, and toluene were removed by vacuum distillation

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

Procedure: Monodispersed activated hexaethylene glycol monomethyl ether was prepared analogously to that of monodispersed triethylene glycol as described herein. A 20% phosgene in toluene solution (35 mL, 6.66 g, 67.4 mmol phosgene) was chilled under a N2 atmosphere in an ice/salt water bath. Monodispersed hexaethylene glycol (1.85 mL, 2.0 g, 6.74 mmol) was dissolved in 5 mL anhydrous EtOAc and added to the phosgene solution via syringe. The reaction mixture was kept stirring in the ice bath for one hour, removed and stirred a further 2.5 hours at room temperature. The phosgene, EtOAc, and toluene were removed by vacuum distillation, leaving monodispersed methyl hexaethylene glycol chloroformate as a clear, oily residue. removed The phosgene, EtOAc, and toluene were removed by vacuum distillation