tert-butyl 3-[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]propanoate

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

Procedure: tert-Butyl 3-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}propionate (131 mg, 0.45 mmol) was dissolved in trifluoroacetic acid and left at room temperature for 1 hour. The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane. The deprotected intermediate was dissolved in dichloromethane and treated with N-hydroxysuccinimide (57 mg, 0.49 mmol) and ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed twice with water. The organic phase was dried over MgSO4 and concentrated in vacuo to provide 122 mg (82%). The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane The deprotected intermediate was dissolved in dichloromethane washed twice with water The organic phase was dried over MgSO4 concentrated in vacuo to provide 122 mg (82%)

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

Procedure: tert-Butyl 3-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}propionate (131 mg, 0.45 mmol) was dissolved in trifluoroacetic acid and left at room temperature for 1 hour. The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane. The deprotected intermediate was dissolved in dichloromethane and treated with N-hydroxysuccinimide (57 mg, 0.49 mmol) and ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed twice with water. The organic phase was dried over MgSO4 and concentrated in vacuo to provide 122 mg (82%). The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane The deprotected intermediate was dissolved in dichloromethane washed twice with water The organic phase was dried over MgSO4 concentrated in vacuo to provide 122 mg (82%)

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

Procedure: Triethylene glycol monomethyl ether (1.0 g, 6.1 mmol) and tert-butyl acrylate (390 mg, 3.05 mmol) were dissolved in dry THF and sodium metal (0.7 mg, 0.03 mmol) was added at room temperature. The mixture was stirred for 4 hours and 1 M HCl was added to quench the reaction. The mixture was extracted twice with dichloromethane, and the organic phase was dried over MgSO4 and concentrated in vacuo to provide an oil, which was purified by silica chromatography using ethyl acetate as eluent. The product was an oil, 773 mg (44%). to quench the reaction The mixture was extracted twice with dichloromethane the organic phase was dried over MgSO4 concentrated in vacuo to provide an oil, which was purified by silica chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To tert-butyl 2,5,8,11-tetraoxatetradecan-14-oate (65 g, 222.6 mmol) (example-1), was added p-toluenesulfonic acid (21.16 g, 111 mmol) and water (31.7 mL). The contents were heated to 80° C. and stirred at that temperature for 2 h. The completion of the reaction was monitor by TLC. The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 using sodium hydroxide solution (17.7 g dissolved in 65 mL water). The contents were stirred at 25-30° C. for 10 minutes. Added Ethyl acetate (65 mL×2), stirred and separated the layer. The aqueous layer was cooled to 0 to 5° C. and the pH was adjusted to 3.5 to 4 using 11 N HCl solution and the product was extracted to methylene chloride (120 ml×2). The combined organic layer was washed with water, brine solution and dried over sodium sulphate. The solvent was removed under vacuum to afford 2,5,8,11-tetraoxatetradecan-14-oic acid (40.5 g, 77.1%). The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 The contents were stirred at 25-30° C. for 10 minutes separated the layer The aqueous layer was cooled to 0 to 5° C. the product was extracted to methylene chloride (120 ml×2) The combined organic layer was washed with water, brine solution dried over sodium sulphate The solvent was removed under vacuum

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To tert-butyl 2,5,8,11-tetraoxatetradecan-14-oate (65 g, 222.6 mmol) (example-1), was added p-toluenesulfonic acid (21.16 g, 111 mmol) and water (31.7 mL). The contents were heated to 80° C. and stirred at that temperature for 2 h. The completion of the reaction was monitor by TLC. The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 using sodium hydroxide solution (17.7 g dissolved in 65 mL water). The contents were stirred at 25-30° C. for 10 minutes. Added Ethyl acetate (65 mL×2), stirred and separated the layer. The aqueous layer was cooled to 0 to 5° C. and the pH was adjusted to 3.5 to 4 using 11 N HCl solution and the product was extracted to methylene chloride (120 ml×2). The combined organic layer was washed with water, brine solution and dried over sodium sulphate. The solvent was removed under vacuum to afford 2,5,8,11-tetraoxatetradecan-14-oic acid (40.5 g, 77.1%). The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 The contents were stirred at 25-30° C. for 10 minutes separated the layer The aqueous layer was cooled to 0 to 5° C. the product was extracted to methylene chloride (120 ml×2) The combined organic layer was washed with water, brine solution dried over sodium sulphate The solvent was removed under vacuum

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

Procedure: Triethyleneglycol monomethyl ether (50 g, 304.5 mmol) was taken in tert-butyl acrylate (35.1 g, 274 mmol) and the mixture was stirred for 10 minutes. Sodium methoxide (1.97 g, 36.5 mmol) was added and stirred at ambient temperature for 8-10 hours. The reaction completion was checked by thin layer chromatography (TLC). The reaction mixture was diluted with ethyl acetate (200 mL) and the organic layer was washed with water, saturated brine solution and dried over sodium sulphate. The solvent was evaporated under reduced pressure to obtain tert-butyl 2,5,8,11-tetraoxatetradecan-14-oate (67 g, 75.3%). stirred at ambient temperature for 8-10 hours the organic layer was washed with water, saturated brine solution dried over sodium sulphate The solvent was evaporated under reduced pressure

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

Procedure: tert-Butyl 3-{2-[2-(2-Methoxyethoxy)ethoxy]ethoxy}propionate (131 mg, 0.45 mmol) was dissolved in trifluoroacetic acid and left at room temperature for 1 hour. The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane. The deprotected intermediate was dissolved in dichloromethane and treated with N-hydroxysuccinimide (57 mg, 0.49 mmol) and ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (86 mg, 0.45 mmol) and stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane and washed twice with water. The organic phase was dried over MgSO4 and concentrated in vacuo to provide 122 mg (82%). The solvent was removed in vacuo and residual trifluoroacetic acid was removed by evaporation from dioxane The deprotected intermediate was dissolved in dichloromethane washed twice with water The organic phase was dried over MgSO4 concentrated in vacuo to provide 122 mg (82%)

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

Procedure: Triethylene glycol monomethyl ether (1.0 g, 6.1 mmol) and tert-butyl acrylate (390 mg, 3.05 mmol) were dissolved in dry THF and sodium metal (0.7 mg, 0.03 mmol) was added at room temperature. The mixture was stirred for 4 hours and 1 M HCl was added to quench the reaction. The mixture was extracted twice with dichloromethane, and the organic phase was dried over MgSO4 and concentrated in vacuo to provide an oil, which was purified by silica chromatography using ethyl acetate as eluent. The product was an oil, 773 mg (44%). to quench the reaction The mixture was extracted twice with dichloromethane the organic phase was dried over MgSO4 concentrated in vacuo to provide an oil, which was purified by silica chromatography

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To tert-butyl 2,5,8,11-tetraoxatetradecan-14-oate (65 g, 222.6 mmol) (example-1), was added p-toluenesulfonic acid (21.16 g, 111 mmol) and water (31.7 mL). The contents were heated to 80° C. and stirred at that temperature for 2 h. The completion of the reaction was monitor by TLC. The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 using sodium hydroxide solution (17.7 g dissolved in 65 mL water). The contents were stirred at 25-30° C. for 10 minutes. Added Ethyl acetate (65 mL×2), stirred and separated the layer. The aqueous layer was cooled to 0 to 5° C. and the pH was adjusted to 3.5 to 4 using 11 N HCl solution and the product was extracted to methylene chloride (120 ml×2). The combined organic layer was washed with water, brine solution and dried over sodium sulphate. The solvent was removed under vacuum to afford 2,5,8,11-tetraoxatetradecan-14-oic acid (40.5 g, 77.1%). The reaction mixture was cooled to 0° C. and basified to pH 10 to 11 The contents were stirred at 25-30° C. for 10 minutes separated the layer The aqueous layer was cooled to 0 to 5° C. the product was extracted to methylene chloride (120 ml×2) The combined organic layer was washed with water, brine solution dried over sodium sulphate The solvent was removed under vacuum

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

Procedure: Triethyleneglycol monomethyl ether (50 g, 304.5 mmol) was taken in tert-butyl acrylate (35.1 g, 274 mmol) and the mixture was stirred for 10 minutes. Sodium methoxide (1.97 g, 36.5 mmol) was added and stirred at ambient temperature for 8-10 hours. The reaction completion was checked by thin layer chromatography (TLC). The reaction mixture was diluted with ethyl acetate (200 mL) and the organic layer was washed with water, saturated brine solution and dried over sodium sulphate. The solvent was evaporated under reduced pressure to obtain tert-butyl 2,5,8,11-tetraoxatetradecan-14-oate (67 g, 75.3%). stirred at ambient temperature for 8-10 hours the organic layer was washed with water, saturated brine solution dried over sodium sulphate The solvent was evaporated under reduced pressure