1,3-dioxane

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: 20 mL of concentrated hydrochloric acid was added to a solution of 1-cyano-1-(trans-4-methoxycyclohexyl)-4-decanol (49) (5.1 g, 17.4 mmol) obtained in the third step dissolved in 200 mL of 1,3-dioxane, and refluxed under heating for 20 hours. The reaction mixture was cooled to room temperature and then put in 100 mL of water, and then extracted with 100 mL of ethyl acetate. The resulting organic layer was washed with water (100 mL×2) and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) and then recrystallized from heptane to obtain 3-(trans-4-methoxycyclohexyl)-6-hexyl-tetrahydro-2-pyranone (Compound No. 25) (2.1 g, 6.9 mmol). The resulting compound was in the form of a colorless liquid, and the yield based on the compound (49) was 40%. obtained in the third step refluxed under heating for 20 hours extracted with 100 mL of ethyl acetate The resulting organic layer was washed with water (100 mL×2) dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) recrystallized from heptane

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

実験手順: 20 mL of concentrated hydrochloric acid was added to a solution of 1-cyano-1-(trans-4-methoxycyclohexyl)-4-decanol (49) (5.1 g, 17.4 mmol) obtained in the third step dissolved in 200 mL of 1,3-dioxane, and refluxed under heating for 20 hours. The reaction mixture was cooled to room temperature and then put in 100 mL of water, and then extracted with 100 mL of ethyl acetate. The resulting organic layer was washed with water (100 mL×2) and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) and then recrystallized from heptane to obtain 3-(trans-4-methoxycyclohexyl)-6-hexyl-tetrahydro-2-pyranone (Compound No. 25) (2.1 g, 6.9 mmol). The resulting compound was in the form of a colorless liquid, and the yield based on the compound (49) was 40%. obtained in the third step refluxed under heating for 20 hours extracted with 100 mL of ethyl acetate The resulting organic layer was washed with water (100 mL×2) dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) recrystallized from heptane

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 1,3-dioxan (3 ml, 0.035 mmol) and acetic anhydride (3.3 ml, 0.035 mmol) at 0° C., was added a drop of concentrated sulphuric acid. The mixture was then stirred for 14 h at 20° C., added with sodium acetate (2 g) and filtrated. The residue, distilled in vacuo (120° C., 16 mmHg), gave 1-acetoxy-3-acetoxymethoxypropane (3.34 g, 50%) as a colorless oil. filtrated The residue, distilled in vacuo (120° C., 16 mmHg)

反応条件: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of 1,3-dioxan (3 ml, 0.035 mmol) and acetic anhydride (3.3 ml, 0.035 mmol) at 0° C., was added a drop of concentrated sulphuric acid. The mixture was then stirred for 14 h at 20° C., added with sodium acetate (2 g) and filtrated. The residue, distilled in vacuo (120° C., 16 mmHg), gave 1-acetoxy-3-acetoxymethoxypropane (3.34 g, 50%) as a colorless oil. filtrated The residue, distilled in vacuo (120° C., 16 mmHg)

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

実験手順: 20 mL of concentrated hydrochloric acid was added to a solution of 1-cyano-1-(trans-4-methoxycyclohexyl)-4-decanol (49) (5.1 g, 17.4 mmol) obtained in the third step dissolved in 200 mL of 1,3-dioxane, and refluxed under heating for 20 hours. The reaction mixture was cooled to room temperature and then put in 100 mL of water, and then extracted with 100 mL of ethyl acetate. The resulting organic layer was washed with water (100 mL×2) and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) and then recrystallized from heptane to obtain 3-(trans-4-methoxycyclohexyl)-6-hexyl-tetrahydro-2-pyranone (Compound No. 25) (2.1 g, 6.9 mmol). The resulting compound was in the form of a colorless liquid, and the yield based on the compound (49) was 40%. obtained in the third step refluxed under heating for 20 hours extracted with 100 mL of ethyl acetate The resulting organic layer was washed with water (100 mL×2) dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The resulting residue was purified by column chromatography (developing solvent: heptane/ethyl acetate=20/1, column packing: silica gel) recrystallized from heptane

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: 1,3-Dioxane, 2-boc amino (10C) (18 mg, 0.05 mmol) and 10 mol % TsOH (1.0 mg, 0.005 mmol) were combined in 5.0 mL 80% EtOH (in H2O) and stirred at reflux for 1 h, until the starting material was consumed as indicated by TLC (5:3/CH2Cl2:EtOAc). The reaction mixture was quenched with 5% NaHCO3, and removed in vacuo. Purification by flash column chromatography on silica gel afforded the desired product as a white solid (92%). at reflux for 1 h, until the starting material was consumed The reaction mixture was quenched with 5% NaHCO3 removed in vacuo Purification by flash column chromatography on silica gel

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

実験手順: 1,3-Dioxane, 2-boc amino (10C) (18 mg, 0.05 mmol) and 10 mol % TsOH (1.0 mg, 0.005 mmol) were combined in 5.0 mL 80% EtOH (in H2O) and stirred at reflux for 1 h, until the starting material was consumed as indicated by TLC (5:3/CH2Cl2:EtOAc). The reaction mixture was quenched with 5% NaHCO3, and removed in vacuo. Purification by flash column chromatography on silica gel afforded the desired product as a white solid (92%). at reflux for 1 h, until the starting material was consumed The reaction mixture was quenched with 5% NaHCO3 removed in vacuo Purification by flash column chromatography on silica gel

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

実験手順: 1,3-Dioxane, 2-boc amino (10B) and 10 mol % TsOH were combined in 5.0 mL THF and 5.0 mL H2O and stirred at reflux until the starting material was consumed as indicated by TLC. The reaction mixture was quenched with 5% NaHCO3 and extracted with CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4, and removed in vacuo. Purification by flash chromatography on silica gel afforded the desired product as a white solid (95%). at reflux until the starting material was consumed The reaction mixture was quenched with 5% NaHCO3 extracted with CH2Cl2 The combined organic layers were dried over anhydrous Na2SO4 removed in vacuo Purification by flash chromatography on silica gel

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

実験手順: 1,3-Dioxane, 2-boc amino (10B) and 10 mol % TsOH were combined in 5.0 mL THF and 5.0 mL H2O and stirred at reflux until the starting material was consumed as indicated by TLC. The reaction mixture was quenched with 5% NaHCO3 and extracted with CH2Cl2. The combined organic layers were dried over anhydrous Na2SO4, and removed in vacuo. Purification by flash chromatography on silica gel afforded the desired product as a white solid (95%). at reflux until the starting material was consumed The reaction mixture was quenched with 5% NaHCO3 extracted with CH2Cl2 The combined organic layers were dried over anhydrous Na2SO4 removed in vacuo Purification by flash chromatography on silica gel

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

実験手順: The new route to Michael acceptors enabled expansion of the structural diversity of these intermediates. Diethoxymethyl Michael acceptor 1b was prepared from commercially available diethoxyacetonitrile in analogy with the synthesis of 1a. Transacetalization of diethoxyacetal 1b with 1,3-propanediol in benzene/TsOH afforded 1,3-dioxane 1c in 64% yield. On the other hand, attempted transacetalization of 1b with ethylene glycol gave an inseparable mixture consisting of 1,3-dioxolane 1d and a by-product assumed to be bis(1,3-dioxolane) C (Scheme 6). Transacetalization of diethoxyacetonitrile with ethylene glycol in the presence of TsOH also did not proceed. Therefore, we considered an alternative approach to 1d.