2,2-dimethyl-5-(phenylmethoxymethyl)-1,3-dioxane

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 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane (3.40 g, 14.4 mmol) and a few crystals of p-toluenesulfonic acid monohydrate in 100 mL of methanol was stirred at room temperature for 20 h. The methanol was removed in vacuo and the residual oil purified by column chromatography on silica gel (ethyl acetate) to give 2.25 g (80%) of 2-benzyloxymethyl-1,3-propanediol as a colorless, clear liquid. The methanol was removed in vacuo the residual oil purified by column chromatography on silica gel (ethyl acetate)

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

Procedure: A mixture of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane (3.40 g, 14.4 mmol) and a few crystals of p-toluenesulfonic acid monohydrate in 100 mL of methanol was stirred at room temperature for 20 h. The methanol was removed in vacuo and the residual oil purified by column chromatography on silica gel (ethyl acetate) to give 2.25 g (80%) of 2-benzyloxymethyl-1,3-propanediol as a colorless, clear liquid. The methanol was removed in vacuo the residual oil purified by column chromatography on silica gel (ethyl acetate)

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

Procedure: A solution of 5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (cf:Bates, H. A.; Farina, J.; Tong, M. J. Org. Chem. 1986, 51, 2637, 3.0 g, 20.5 mmol) in 25 mL of dry DME under argon was added via cannula to a slurry of NaH (0.740 g, 80% dispersion in oil, 24.6 mmol) in 60 mL of dry DME cooled to 0° C. The resulting grey slurry was stirred at room temperature for 0.5 h, then recooled to 0° C., and treated with a solution of benzylbromide (4.56 g, 26.7 mmol) in 20 mL of DME. The reaction mixture was stirred at room temperature (rt) overnight and then quenched with 100 ml of H2O. The aqueous layer was separated and extracted with two portions of ethyl acetate. The combined organic layers were then washed with saturated sodium chloride solution, dried over MgSO4, filtered, and concentrated to provide a yellow oil. Purification by column chromatography on silica gel (ethyl acetate/hexane) afforded 3.51 g (72%) of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane as a clear colorless liquid. recooled to 0° C. The reaction mixture was stirred at room temperature (rt) overnight quenched with 100 ml of H2O The aqueous layer was separated extracted with two portions of ethyl acetate The combined organic layers were then washed with saturated sodium chloride solution dried over MgSO4 filtered concentrated to provide a yellow oil Purification by column chromatography on silica gel (ethyl acetate/hexane)

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

Procedure: A solution of 5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (cf:Bates, H. A.; Farina, J.; Tong, M. J. Org. Chem. 1986, 51, 2637, 3.0 g, 20.5 mmol) in 25 mL of dry DME under argon was added via cannula to a slurry of NaH (0.740 g, 80% dispersion in oil, 24.6 mmol) in 60 mL of dry DME cooled to 0° C. The resulting grey slurry was stirred at room temperature for 0.5 h, then recooled to 0° C., and treated with a solution of benzylbromide (4.56 g, 26.7 mmol) in 20 mL of DME. The reaction mixture was stirred at room temperature (rt) overnight and then quenched with 100 ml of H2O. The aqueous layer was separated and extracted with two portions of ethyl acetate. The combined organic layers were then washed with saturated sodium chloride solution, dried over MgSO4, filtered, and concentrated to provide a yellow oil. Purification by column chromatography on silica gel (ethyl acetate/hexane) afforded 3.51 g (72%) of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane as a clear colorless liquid. recooled to 0° C. The reaction mixture was stirred at room temperature (rt) overnight quenched with 100 ml of H2O The aqueous layer was separated extracted with two portions of ethyl acetate The combined organic layers were then washed with saturated sodium chloride solution dried over MgSO4 filtered concentrated to provide a yellow oil Purification by column chromatography on silica gel (ethyl acetate/hexane)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium hydride (2.0 g, 42.02 mmol, 50% dispersion in oil) in tetrahydrofuran (20.0 ml) was added dropwise a solution of (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (4.09 g, 28.01 mmol) in tetrahydrofuran (10 ml) at 0° C. it was then stirred at 0° C. for 10 min and at 25° C. for 20 min. After that time, the reaction was cooled back to 0° C. and benzyl bromide (4.7 ml, 39.22 mmol) and tetrabutylammonium iodide (0.1 g, 0.27 mmol) were added. The reaction was stirred overnight at 25° C. After such time, the reaction was diluted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered and then concentrated in vacuo. Purification on an AnaLogix Intelliflash system (120 g column, 15% ethyl acetate/hexanes to 25% ethyl acetate/hexanes) afforded 5-benzyloxymethyl-2,2-dimethyl-[1,3]dioxane (5.28 g, 80%) as a clear oil: 1H NMR (300 MHz, CDCl3) δ ppm 1.40 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.97-2.09 (m, 1H, CH), 3.53 (d, J=6.8 Hz, 2H, OCH2), 3.79 (dd, Jgem=11.9 Hz, J=6.4 Hz, 2H, 2×OCH of 2×OCH2), 3.98 (dd, Jgem=11.9 Hz, J=4.3 Hz, 2H, 2×OCH of 2×OCH2), 4.52 (s, 2H, OCH2Ar), 7.27-7.39 (m, 5H, Ar). After that time, the reaction was cooled back to 0° C. The reaction was stirred overnight at 25° C washed with water The organic layer was dried over magnesium sulfate filtered concentrated in vacuo Purification on an AnaLogix Intelliflash system (120 g column, 15% ethyl acetate/hexanes to 25% ethyl acetate/hexanes)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred suspension of sodium hydride (2.0 g, 42.02 mmol, 50% dispersion in oil) in tetrahydrofuran (20.0 ml) was added dropwise a solution of (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (4.09 g, 28.01 mmol) in tetrahydrofuran (10 ml) at 0° C. it was then stirred at 0° C. for 10 min and at 25° C. for 20 min. After that time, the reaction was cooled back to 0° C. and benzyl bromide (4.7 ml, 39.22 mmol) and tetrabutylammonium iodide (0.1 g, 0.27 mmol) were added. The reaction was stirred overnight at 25° C. After such time, the reaction was diluted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate, filtered and then concentrated in vacuo. Purification on an AnaLogix Intelliflash system (120 g column, 15% ethyl acetate/hexanes to 25% ethyl acetate/hexanes) afforded 5-benzyloxymethyl-2,2-dimethyl-[1,3]dioxane (5.28 g, 80%) as a clear oil: 1H NMR (300 MHz, CDCl3) δ ppm 1.40 (s, 3H, CH3), 1.43 (s, 3H, CH3), 1.97-2.09 (m, 1H, CH), 3.53 (d, J=6.8 Hz, 2H, OCH2), 3.79 (dd, Jgem=11.9 Hz, J=6.4 Hz, 2H, 2×OCH of 2×OCH2), 3.98 (dd, Jgem=11.9 Hz, J=4.3 Hz, 2H, 2×OCH of 2×OCH2), 4.52 (s, 2H, OCH2Ar), 7.27-7.39 (m, 5H, Ar). After that time, the reaction was cooled back to 0° C. The reaction was stirred overnight at 25° C washed with water The organic layer was dried over magnesium sulfate filtered concentrated in vacuo Purification on an AnaLogix Intelliflash system (120 g column, 15% ethyl acetate/hexanes to 25% ethyl acetate/hexanes)

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

Procedure: A mixture of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane (3.40 g, 14.4 mmol) and a few crystals of p-toluenesulfonic acid monohydrate in 100 mL of methanol was stirred at room temperature for 20 h. The methanol was removed in vacuo and the residual oil purified by column chromatography on silica gel (ethyl acetate) to give 2.25 g (80%) of 2-benzyloxymethyl-1,3-propanediol as a colorless, clear liquid. The methanol was removed in vacuo the residual oil purified by column chromatography on silica gel (ethyl acetate)

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

Procedure: A solution of 5-hydroxymethyl-2,2-dimethyl-1,3-dioxane (cf:Bates, H. A.; Farina, J.; Tong, M. J. Org. Chem. 1986, 51, 2637, 3.0 g, 20.5 mmol) in 25 mL of dry DME under argon was added via cannula to a slurry of NaH (0.740 g, 80% dispersion in oil, 24.6 mmol) in 60 mL of dry DME cooled to 0° C. The resulting grey slurry was stirred at room temperature for 0.5 h, then recooled to 0° C., and treated with a solution of benzylbromide (4.56 g, 26.7 mmol) in 20 mL of DME. The reaction mixture was stirred at room temperature (rt) overnight and then quenched with 100 ml of H2O. The aqueous layer was separated and extracted with two portions of ethyl acetate. The combined organic layers were then washed with saturated sodium chloride solution, dried over MgSO4, filtered, and concentrated to provide a yellow oil. Purification by column chromatography on silica gel (ethyl acetate/hexane) afforded 3.51 g (72%) of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane as a clear colorless liquid. recooled to 0° C. The reaction mixture was stirred at room temperature (rt) overnight quenched with 100 ml of H2O The aqueous layer was separated extracted with two portions of ethyl acetate The combined organic layers were then washed with saturated sodium chloride solution dried over MgSO4 filtered concentrated to provide a yellow oil Purification by column chromatography on silica gel (ethyl acetate/hexane)

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

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Boron trifluoride-diethyl ether complex (0,9 ml,0.007 ml) was dropped in benzyl alcohol (92 ml) of glycidol (22.01 g, 0.3 mol) on ice bath. After dropping the mixture was stirred for 8 hours at 25° C. After the reaction was over, triethylamine was added thereto and benzyl alcohol was removed in vacuo. The desidue was dissolved in acetone and thereto p-toluenesulfonic acid was added. The mixture was reacted for 8 hours at 25° C. After the completion of the reaction triethylamine was added thereto and acetone was removed in vacuo. The crude product was distilled to give a mixture (43.8 g, yield 81%) of 4-benzyloxymethyl-2,2-dimethyl-1,3-dioxolane and 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane. The ratio of the dioxolane and the dioxane was 8 to 1 by analysis with gas chromatography. was added benzyl alcohol was removed in vacuo The desidue was dissolved in acetone p-toluenesulfonic acid was added The mixture was reacted for 8 hours at 25° C was added acetone was removed in vacuo The crude product was distilled

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

Procedure: A mixture of 5-benzyloxymethyl-2,2-dimethyl-1,3-dioxane (3.40 g, 14.4 mmol) and a few crystals of p-toluenesulfonic acid monohydrate in 100 mL of methanol was stirred at room temperature for 20 h. The methanol was removed in vacuo and the residual oil purified by column chromatography on silica gel (ethyl acetate) to give 2.25 g (80%) of 2-benzyloxymethyl-1,3-propanediol as a colorless, clear liquid. The methanol was removed in vacuo the residual oil purified by column chromatography on silica gel (ethyl acetate)