[5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methanol

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, benzyl ethers may be used to protect --OH groups. For example, 2,2-dimethyl-4,5-di(hydroxymethyl)-1,3-dioxolane (8 g, 0.2 mol) is heated at reflux with benzyl chloride (25 g, 0.2 mol) and K2CO3 (25 g, 0.2 mol) in 100 mL ethanol. The product is added to aqueous NaOH, extracted with ether, and purified by silica gel chromatography to yield 2,2-dimethyl-4-hydroxymethyl-5-benzyloxymethyl-1,3-dioxolane. extracted with ether purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, benzyl ethers may be used to protect --OH groups. For example, 2,2-dimethyl-4,5-di(hydroxymethyl)-1,3-dioxolane (8 g, 0.2 mol) is heated at reflux with benzyl chloride (25 g, 0.2 mol) and K2CO3 (25 g, 0.2 mol) in 100 mL ethanol. The product is added to aqueous NaOH, extracted with ether, and purified by silica gel chromatography to yield 2,2-dimethyl-4-hydroxymethyl-5-benzyloxymethyl-1,3-dioxolane. extracted with ether purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (4.0 g, 60% dispersion in oil) in tetrahydrofuran (150 mL) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4,5-dimethanol (VII, 4.05 g) in tetrahydrofuran (25 mL) over 2 min at room temperature, followed by solid tetrabutylammonium hydrogen sulfate (0.4 g). The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 8.1 g) in tetrahydrofuran (25 mL) was added dropwise over a period of 15 min. The reaction mixture was warmed to room temperature over 1 h then refluxed for 6 h. On cooling to room temperature, the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×30 mL). The combined organic fractions was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent, thereby affording the title compound (IX 4.5 g) as an oil and the mono O-alkylated compound, 4-(2-chlorophenyl)-2-(5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy-methyl-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (X, 1.95 g). Compound IX. IR (neat, cm-1): 1723, 1636; MS (CI): 436 (100%, [M+NH4 ]+). Compound X. IR (neat, cm-1): 3455, 1734; The resulting mixture was cooled in an ice bath then refluxed for 6 h On cooling to room temperature the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure The aqueous phase was extracted with ethyl acetate (3×30 mL) The combined organic fractions was washed with brine dried (sodium sulfate) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (4.0 g, 60% dispersion in oil) in tetrahydrofuran (150 mL) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4,5-dimethanol (VII, 4.05 g) in tetrahydrofuran (25 mL) over 2 min at room temperature, followed by solid tetrabutylammonium hydrogen sulfate (0.4 g). The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 8.1 g) in tetrahydrofuran (25 mL) was added dropwise over a period of 15 min. The reaction mixture was warmed to room temperature over 1 h then refluxed for 6 h. On cooling to room temperature, the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×30 mL). The combined organic fractions was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent, thereby affording the title compound (IX 4.5 g) as an oil and the mono O-alkylated compound, 4-(2-chlorophenyl)-2-(5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy-methyl-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (X, 1.95 g). Compound IX. IR (neat, cm-1): 1723, 1636; MS (CI): 436 (100%, [M+NH4 ]+). Compound X. IR (neat, cm-1): 3455, 1734; The resulting mixture was cooled in an ice bath then refluxed for 6 h On cooling to room temperature the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure The aqueous phase was extracted with ethyl acetate (3×30 mL) The combined organic fractions was washed with brine dried (sodium sulfate) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, benzyl ethers may be used to protect --OH groups. For example, 2,2-dimethyl-4,5-di(hydroxymethyl)-1,3-dioxolane (8 g, 0.2 mol) is heated at reflux with benzyl chloride (25 g, 0.2 mol) and K2CO3 (25 g, 0.2 mol) in 100 ml ethanol. The product is added to aqueous NaOH, extracted with ether, and purified by silica gel chromatography to yield 2,2-dimethyl-4-hydroxymethyl-5-benzyloxymethyl-1,3-dioxolane. extracted with ether purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Alternatively, benzyl ethers may be used to protect --OH groups. For example, 2,2-dimethyl-4,5-di(hydroxymethyl)-1,3-dioxolane (8 g, 0.2 mol) is heated at reflux with benzyl chloride (25 g, 0.2 mol) and K2CO3 (25 g, 0.2 mol) in 100 mL ethanol. The product is added to aqueous NaOH, extracted with ether, and purified by silica gel chromatography to yield 2,2-dimethyl-4-hydroxymethyl-5-benzyloxymethyl-1,3-dioxolane. extracted with ether purified by silica gel chromatography

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of sodium hydride (4.0 g, 60% dispersion in oil) in tetrahydrofuran (150 mL) under a nitrogen atmosphere was added a solution of 2,2-dimethyl-[1,3]dioxolane-4,5-dimethanol (VII, 4.05 g) in tetrahydrofuran (25 mL) over 2 min at room temperature, followed by solid tetrabutylammonium hydrogen sulfate (0.4 g). The resulting mixture was cooled in an ice bath and a solution of ethyl 4-chloroacetoacetate (VIII, 8.1 g) in tetrahydrofuran (25 mL) was added dropwise over a period of 15 min. The reaction mixture was warmed to room temperature over 1 h then refluxed for 6 h. On cooling to room temperature, the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure. The aqueous phase was extracted with ethyl acetate (3×30 mL). The combined organic fractions was washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) using a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent, thereby affording the title compound (IX 4.5 g) as an oil and the mono O-alkylated compound, 4-(2-chlorophenyl)-2-(5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy-methyl-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid 3-ethyl 5-methyl ester (X, 1.95 g). Compound IX. IR (neat, cm-1): 1723, 1636; MS (CI): 436 (100%, [M+NH4 ]+). Compound X. IR (neat, cm-1): 3455, 1734; The resulting mixture was cooled in an ice bath then refluxed for 6 h On cooling to room temperature the reaction mixture was quenched with 1N hydrochloric acid (20 mL) and volatile materials were removed under reduced pressure The aqueous phase was extracted with ethyl acetate (3×30 mL) The combined organic fractions was washed with brine dried (sodium sulfate) filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel (grade 9385, Merck, 230-400 mesh, 60 Å) a mixture of hexane and ethyl acetate (8:2, 7:3 and 6:4; 500 mL each) as eluent