ethyl 3-(2-methyl-1,3-dioxolan-2-yl)propanoate

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:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of about 34.35 g of isopropylcyclohexylamine in about 150 ml of tetrahydrofuran at about -20° C. was added about 156.89 ml of an about 1.55M n-butyllithium, at a rate so that the final temperature reached about 10° C. The solution was then cooled to about -70° C. and about 25 g of ethyl levulinate ethylene ketal was added dropwise. After about 15 minutes, the solution was warmed to about -30° C. and maintained at that temperature while it was added rapidly, dropwise to a stirred solution of about 80.44 g of octadecyl iodide in about 150 ml of dimethyl sulfoxide and about 50 ml of tetrahydrofuran at room temperature. This mixture was stirred overnight, the volatile solvents were removed and water was added. The resulting solid was collected by filtration and extracted with ether giving a solution and a solid. This solution and original filtrate were combined and extracted with ether. This ether extract was dried and the solvent removed giving an oil. This oil was subjected to HPLC, eluting with hexane:ether (about 9:1). The product band was collected and the solvent removed, giving about 30.76 g of the desired title compound as a solid, mp 33°-34° C. reached about 10° C the solution was warmed to about -30° C. maintained at that temperature while it the volatile solvents were removed water was added The resulting solid was collected by filtration extracted with ether giving a solution extracted with ether This ether extract was dried the solvent removed giving an oil eluting with hexane The product band was collected the solvent removed

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

Procedure: A mixture of about 33 g of 1-(bromomethyl)-4-(tetradecyloxy)benzene, about 16.2 g of ethyl levulinate ethylene ketal, about 4.54 g of about 50% sodium hydride and about 350 ml of tetrahydrofuran was refluxed with stirring, under argon for about 18 hours and then filtered through celite. The solvent was removed and the residue was dissolved in ether. The ether solution was washed with aqueous monobasic sodium phosphate, dried and the solvent removed. The residue was subjected to high performance liquid chromatography (HPLC), using the system hexane:ethyl acetate (about 9:1), giving about 22.1 g of the desired title compound as a light yellow oil). was refluxed filtered through celite The solvent was removed the residue was dissolved in ether The ether solution was washed with aqueous monobasic sodium phosphate dried the solvent removed

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

Procedure: A mixture of about 110.86 g of ethylene glycol, about 2 g of p-toluenesulfonic acid and about 800 ml of toluene was refluxed using a Dean-Stark trap until no more water came off. An about 250 g portion of ethyl levulinate was added and refluxing was continued until no more water came off. The mixture was then cooled to room temperature, poured into saturated sodium bicarbonate, the organic layer dried and the solvent removed. The residue was distilled (about 67°-70° C., 0.35 mm) and the distillate stirred for about 20 minutes with about 6 g of sodium borohydride in ethanol. The solvent was removed, the residue dissolved in ether, washed with saturated sodium bicarbonate, dried and then distilled (about 41°-45° C., 0.3 mm), giving about 83 g of the desired title compound. was refluxed refluxing the organic layer dried the solvent removed The residue was distilled (about 67°-70° C., 0.35 mm) The solvent was removed the residue dissolved in ether washed with saturated sodium bicarbonate dried distilled (about 41°-45° C., 0.3 mm)

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of about 34.35 g of isopropylcyclohexylamine in about 150 ml of tetrahydrofuran at about -20° C. was added about 156.89 ml of an about 1.55M n-butyllithium, at a rate so that the final temperature reached about 10° C. The solution was then cooled to about -70° C. and about 25 g of ethyl levulinate ethylene ketal was added dropwise. After about 15 minutes, the solution was warmed to about -30° C. and maintained at that temperature while it was added rapidly, dropwise to a stirred solution of about 80.44 g of octadecyl iodide in about 150 ml of dimethyl sulfoxide and about 50 ml of tetrahydrofuran at room temperature. This mixture was stirred overnight, the volatile solvents were removed and water was added. The resulting solid was collected by filtration and extracted with ether giving a solution and a solid. This solution and original filtrate were combined and extracted with ether. This ether extract was dried and the solvent removed giving an oil. This oil was subjected to HPLC, eluting with hexane:ether (about 9:1). The product band was collected and the solvent removed, giving about 30.76 g of the desired title compound as a solid, mp 33°-34° C. reached about 10° C the solution was warmed to about -30° C. maintained at that temperature while it the volatile solvents were removed water was added The resulting solid was collected by filtration extracted with ether giving a solution extracted with ether This ether extract was dried the solvent removed giving an oil eluting with hexane The product band was collected the solvent removed

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

Procedure: A mixture of about 33 g of 1-(bromomethyl)-4-(tetradecyloxy)benzene, about 16.2 g of ethyl levulinate ethylene ketal, about 4.54 g of about 50% sodium hydride and about 350 ml of tetrahydrofuran was refluxed with stirring, under argon for about 18 hours and then filtered through celite. The solvent was removed and the residue was dissolved in ether. The ether solution was washed with aqueous monobasic sodium phosphate, dried and the solvent removed. The residue was subjected to high performance liquid chromatography (HPLC), using the system hexane:ethyl acetate (about 9:1), giving about 22.1 g of the desired title compound as a light yellow oil). was refluxed filtered through celite The solvent was removed the residue was dissolved in ether The ether solution was washed with aqueous monobasic sodium phosphate dried the solvent removed

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

Procedure: A mixture of about 110.86 g of ethylene glycol, about 2 g of p-toluenesulfonic acid and about 800 ml of toluene was refluxed using a Dean-Stark trap until no more water came off. An about 250 g portion of ethyl levulinate was added and refluxing was continued until no more water came off. The mixture was then cooled to room temperature, poured into saturated sodium bicarbonate, the organic layer dried and the solvent removed. The residue was distilled (about 67°-70° C., 0.35 mm) and the distillate stirred for about 20 minutes with about 6 g of sodium borohydride in ethanol. The solvent was removed, the residue dissolved in ether, washed with saturated sodium bicarbonate, dried and then distilled (about 41°-45° C., 0.3 mm), giving about 83 g of the desired title compound. was refluxed refluxing the organic layer dried the solvent removed The residue was distilled (about 67°-70° C., 0.35 mm) The solvent was removed the residue dissolved in ether washed with saturated sodium bicarbonate dried distilled (about 41°-45° C., 0.3 mm)

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

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

Procedure: A solution of ethyl 3-(2-methyl-1,3-dioxolan-2-yl)propanoate (68.9 g, 366 mmol) in methanol (73 mL) was cooled to approximately 0° C. A warm solution of sodium hydroxide (14.63 g, 366 mmol) in water (73 mL) was added dropwise over a period of three hours. The reaction was then allowed to warm to room temperature and stirred for 17 hours. The methanol was removed under reduced pressure, and the resulting aqueous solution was diluted with water (400 mL) and washed with ethyl acetate (150 mL). The aqueous solution was then cooled to approximately 0° C. and adjusted to pH 2 with the addition of sulfuric acid (180 mL of 1 M). The resulting mixture was extracted with ethyl acetate (2×150 mL), and the combined extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 38.6 g of 3-(2-methyl-1,3-dioxolan-2-yl)propanoic acid as a light yellow oil. The methanol was removed under reduced pressure the resulting aqueous solution was diluted with water (400 mL) washed with ethyl acetate (150 mL) The aqueous solution was then cooled to approximately 0° C. adjusted to pH 2 with the addition of sulfuric acid (180 mL of 1 M) The resulting mixture was extracted with ethyl acetate (2×150 mL) the combined extracts were washed with brine (50 mL) dried over sodium sulfate filtered concentrated under reduced pressure

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

Procedure: A solution of ethyl 3-(2-methyl-1,3-dioxolan-2-yl)propanoate (68.9 g, 366 mmol) in methanol (73 mL) was cooled to approximately 0° C. A warm solution of sodium hydroxide (14.63 g, 366 mmol) in water (73 mL) was added dropwise over a period of three hours. The reaction was then allowed to warm to room temperature and stirred for 17 hours. The methanol was removed under reduced pressure, and the resulting aqueous solution was diluted with water (400 mL) and washed with ethyl acetate (150 mL). The aqueous solution was then cooled to approximately 0° C. and adjusted to pH 2 with the addition of sulfuric acid (180 mL of 1 M). The resulting mixture was extracted with ethyl acetate (2×150 mL), and the combined extracts were washed with brine (50 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 38.6 g of 3-(2-methyl-1,3-dioxolan-2-yl)propanoic acid as a light yellow oil. The methanol was removed under reduced pressure the resulting aqueous solution was diluted with water (400 mL) washed with ethyl acetate (150 mL) The aqueous solution was then cooled to approximately 0° C. adjusted to pH 2 with the addition of sulfuric acid (180 mL of 1 M) The resulting mixture was extracted with ethyl acetate (2×150 mL) the combined extracts were washed with brine (50 mL) dried over sodium sulfate filtered concentrated under reduced pressure