2-[2-[2-(2-methoxyethoxy)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:; See reaction.notes.procedure_details.

Procedure: A mixture of 12.9 g. (62 mmoles) of tetraethylene glycol monomethyl ether and 4.9 g. (62 mmoles) of pyridine is added dropwise to 77 ml. (124 mmoles) of a 17.2% solution of phosgene in benzene stirred in an ice bath with protection from moisture. The pyridine hydrochloride precipitates during the 35 to 40 minute addition and stirring is continued in the ice bath for an additional 2 hours. The reaction mixture is allowed to warm to room temperature and stirred overnight. The benzene solution is decanted from the pyridine hydrochloride which is washed with additional benzene. A stream of nitrogen is passed through the solution to remove excess phosgene as well as most of the benzene. The residual oil is dissolved in benzene-hexane and filtered to remove additional pyridine hydrochloride. The filtrate is evaporated to dryness in vacuo affording 17.1 g. of a residual oil, the infrared analysis of which reveals a strong carbonyl absorption and minimal hydroxyl absorption. The oil is used as is in the next step. A mixture of 12.9 g The pyridine hydrochloride precipitates during the 35 to 40 minute addition stirred overnight The benzene solution is decanted from the pyridine hydrochloride which is washed with additional benzene to remove excess phosgene as well as most of the benzene The residual oil is dissolved in benzene-hexane filtered to remove additional pyridine hydrochloride The filtrate is evaporated to dryness in vacuo affording 17.1 g a strong carbonyl absorption and minimal hydroxyl absorption

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: Tetraethylene glycol monomethyl ether (1.0 g, 4.8 mmol) and N,N′-disuccinimidyl carbonate (1.48 g, 5.8 mmol) were dissolved in acetonitrile (10 mL). Then triethylamine (1.0 mL, 7.2 mmol) was added and the reaction stirred overnight at room temperature. Crude reaction was evaporated to dryness, dissolved in sat. NaHCO3 (30 mL), washed ethyl acetate (2×30 mL), dried MgSO4, and evaporated to dryness. Column chromatography (Silica, ethyl acetate/MeOH, 20:1) afforded 1 a clear oil (0.462 g, 28% yield). Crude reaction was evaporated to dryness dissolved in sat. NaHCO3 (30 mL) washed ethyl acetate (2×30 mL), dried MgSO4 evaporated to dryness

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

Procedure: An oven-dried 100 mL round bottom flask was charged with t-BuOK (13 mmol), dry THF (30 mL), purged with argon and cooled to 0° C. in an ice bath. Tetraethyleneglycol monomethyl ether (10 mmol) was then added dropwise to the solution and the reaction stirred at 0° C. for 1 h under argon. Allyl bromide (13 mmol) was added dropwise, and the solution was warmed to R.T. and allowed to stir for 24 h under argon. Deionized water (2 mL) was then added and the reaction stirred for 10 min. All liquid were then removed in vacuo and the residue redissolved in ethyl acetate (50 mL). The organic was washed three times with water (20 mL), dried over Na2SO4, filtered over Celite and then concentrated in vacuo to yield clear/light yellow oil (47%). 1HNMR (400 MHz, CDCl3): δ=5.90 (m, 1H), 5.23 (dd, 1H, 3JHHtrans=17.3 Hz, 2JHHgem=1.7 Hz), 5.15 (dd, 1H, 3JHH=10.4 Hz, 2JHHgem=1.5 Hz), 4.00 (dd, 2H, 3JHH=5.89 Hz, 4JHH=1.5 Hz), 3.65 (m, 12H), 3.59 (m, 2H), 3.53 (m, 2H), 3.36 (s 3H) ppm. 13CNMR (400 MHz, CDCl3): δ=134.8, 117.0, 72.2, 71.9, 70.6, 70.6, 70.6, 70.5, 69.4, 59.0 ppm. HRMS-ESI: Calculated [M+Na]+: 271.1516. found: 271.1516. purged with argon the solution was warmed to R.T. to stir for 24 h under argon the reaction stirred for 10 min All liquid were then removed in vacuo the residue redissolved in ethyl acetate (50 mL) The organic was washed three times with water (20 mL) dried over Na2SO4 filtered over Celite concentrated in vacuo

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

Procedure: An oven-dried 100 mL round bottom flask was charged with t-BuOK (13 mmol), dry THF (30 mL), purged with argon and cooled to 0° C. in an ice bath. Tetraethyleneglycol monomethyl ether (10 mmol) was then added dropwise to the solution and the reaction stirred at 0° C. for 1 h under argon. Allyl bromide (13 mmol) was added dropwise, and the solution was warmed to R.T. and allowed to stir for 24 h under argon. Deionized water (2 mL) was then added and the reaction stirred for 10 min. All liquid were then removed in vacuo and the residue redissolved in ethyl acetate (50 mL). The organic was washed three times with water (20 mL), dried over Na2SO4, filtered over Celite and then concentrated in vacuo to yield clear/light yellow oil (47%). 1HNMR (400 MHz, CDCl3): δ=5.90 (m, 1H), 5.23 (dd, 1H, 3JHHtrans=17.3 Hz, 2JHHgem=1.7 Hz), 5.15 (dd, 1H, 3JHH=10.4 Hz, 2JHHgem=1.5 Hz), 4.00 (dd, 2H, 3JHH=5.89 Hz, 4JHH=1.5 Hz), 3.65 (m, 12H), 3.59 (m, 2H), 3.53 (m, 2H), 3.36 (s 3H) ppm. 13CNMR (400 MHz, CDCl3): δ=134.8, 117.0, 72.2, 71.9, 70.6, 70.6, 70.6, 70.5, 69.4, 59.0 ppm. HRMS-ESI: Calculated [M+Na]+: 271.1516. found: 271.1516. purged with argon the solution was warmed to R.T. to stir for 24 h under argon the reaction stirred for 10 min All liquid were then removed in vacuo the residue redissolved in ethyl acetate (50 mL) The organic was washed three times with water (20 mL) dried over Na2SO4 filtered over Celite concentrated in vacuo

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

Procedure: A mixture consisting of 6-fluoro-2,3-dihydro-2',5'-dioxo-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2-carboxylic acid (2.8 g, 0.01 mol) (obtained through the process as described in Example 1), 3,6,9,12-tetraoxatridecanol (2.1 g, 0.01 mol) and p-toluenesulfonic acid (1.9 g, 0.01 mol) in 80 ml of toluene was heated at reflux temperature for 7.0 hours under a Dean-Stark trap. The reaction mixture was evaporated in vacuo to give a semi-solid residue which was partitioned between 50 ml of chloroform and 50 ml of water. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to give a pale yellow oil which was chromatographed on silica gel, eluting with ethyl acetate to give 3.9 g (82.5%) of the desired refined compound as a colorless oil. obtained through the process was heated at reflux temperature for 7.0 hours under a Dean-Stark trap The reaction mixture was evaporated in vacuo to give a semi-solid residue which was partitioned between 50 ml of chloroform and 50 ml of water The organic layer was dried over anhydrous sodium sulfate filtered evaporated in vacuo to give a pale yellow oil which was chromatographed on silica gel eluting with ethyl acetate