methyl cyclopent-3-ene-1-carboxylate

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: The above procedure was repeated except that methyl cyclopent-3-ene carboxylate (prepared as described by A. H. Schmid and A. W. Wolkoff, J. Org. Chem. 32, 254 (1967)) was used with the 6-tetrahydropyranyloxyhexyl bromide of part D of this example and 1-(6-tetrahydropyranyloxyhexyl)-1-hydroxymethylcyclopent-3-ene was obtained as an oil (IR 3400, 3010 cm-1, nmr τ 4.4, 5.4, 6.35, 7.8, 8.5). prepared

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

実験手順: The above procedure was repeated except that methyl cyclopent-3-ene carboxylate (prepared as described by A. H. Schmid and A. W. Wolkoff, J. Org. Chem. 32, 254 (1967)) was used with the 6-tetrahydropyranyloxyhexyl bromide of part D of this example and 1-(6-tetrahydropyranyloxyhexyl)-1-hydroxymethylcyclopent-3-ene was obtained as an oil (IR 3400, 3010 cm-1, nmr τ 4.4, 5.4, 6.35, 7.8, 8.5). prepared

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl cyclopent-3-ene-1-carboxylate (4.42 g, 35 mmol) was dissolved in DCM/MeOH (160 mL, 3:1) and cooled to −78° C. Ozone was passed through the solution until a blue colour persisted. Excess ozone was purged from the reaction mixture with dry N2. Dimethylsulfide (10 mL) was added and the reaction mixture was warmed to rt, the solvent was removed in vacuo. The residue was added to a solution of tert-butyl (4S)-4-aminoazepane-1-carboxylate (7.5 g, 35 mmol), STAB (18.57 g, 87.6 mmol), NEt3 (4.26 g, 42.1 mmol) and acetic acid (1.8 mL) in DCE (200 mL). The mixture was stirred for 3 hours at rt and was then poured into aqueous Na2CO3 solution. The mixture was extracted with EtOAc (3×200 mL), the organic phase were washed with water (100 mL) and brine (100 mL), dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether) to give tert-butyl (4S)-4-[4-(methoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (7.7 g, 64.6% yield) as a yellow oil. Excess ozone was purged from the reaction mixture with dry N2 Dimethylsulfide (10 mL) was added the reaction mixture was warmed to rt the solvent was removed in vacuo The mixture was extracted with EtOAc (3×200 mL) the organic phase were washed with water (100 mL) and brine (100 mL) dried over Na2SO4 The solvent was removed in vacuo the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl cyclopent-3-ene-1-carboxylate (4.42 g, 35 mmol) was dissolved in DCM/MeOH (160 mL, 3:1) and cooled to −78° C. Ozone was passed through the solution until a blue colour persisted. Excess ozone was purged from the reaction mixture with dry N2. Dimethylsulfide (10 mL) was added and the reaction mixture was warmed to rt, the solvent was removed in vacuo. The residue was added to a solution of tert-butyl (4S)-4-aminoazepane-1-carboxylate (7.5 g, 35 mmol), STAB (18.57 g, 87.6 mmol), NEt3 (4.26 g, 42.1 mmol) and acetic acid (1.8 mL) in DCE (200 mL). The mixture was stirred for 3 hours at rt and was then poured into aqueous Na2CO3 solution. The mixture was extracted with EtOAc (3×200 mL), the organic phase were washed with water (100 mL) and brine (100 mL), dried over Na2SO4. The solvent was removed in vacuo, and the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether) to give tert-butyl (4S)-4-[4-(methoxycarbonyl)piperidin-1-yl]azepane-1-carboxylate (7.7 g, 64.6% yield) as a yellow oil. Excess ozone was purged from the reaction mixture with dry N2 Dimethylsulfide (10 mL) was added the reaction mixture was warmed to rt the solvent was removed in vacuo The mixture was extracted with EtOAc (3×200 mL) the organic phase were washed with water (100 mL) and brine (100 mL) dried over Na2SO4 The solvent was removed in vacuo the residue was purified by column chromatography (gradient 0% to 25% EtOAc in Petroleum ether)

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

実験手順: The above procedure was repeated except that methyl cyclopent-3-ene carboxylate (prepared as described by A. H. Schmid and A. W. Wolkoff, J. Org. Chem. 32, 254 (1967)) was used with the 6-tetrahydropyranyloxyhexyl bromide of part D of this example and 1-(6-tetrahydropyranyloxyhexyl)-1-hydroxymethylcyclopent-3-ene was obtained as an oil (IR 3400, 3010 cm-1, nmr τ 4.4, 5.4, 6.35, 7.8, 8.5). prepared

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

実験手順: The above procedure was repeated except that methyl cyclopent-3-ene carboxylate (prepared as described by A. H. Schmid and A. W. Wolkoff, J. Org. Chem. 32, 254 (1967)) was used with the 6-tetrahydropyranyloxyhexyl bromide of part D of this example and 1-(6-tetrahydropyranyloxyhexyl)-1-hydroxymethylcyclopent-3-ene was obtained as an oil (IR 3400, 3010 cm-1, nmr τ 4.4, 5.4, 6.35, 7.8, 8.5). prepared

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

実験手順: The above procedure was repeated except that methyl cyclopent-3-ene carboxylate (prepared as described by A. H. Schmid and A. W. Wolkoff, J. Org. Chem. 32, 254 (1967)) was used with the 6-tetrahydropyranyloxyhexyl bromide of part D of this example and 1-(6-tetrahydropyranyloxyhexyl)-1-hydroxymethylcyclopent-3-ene was obtained as an oil (IR 3400, 3010 cm-1, nmr τ 4.4, 5.4, 6.35, 7.8, 8.5). prepared

反応条件: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of a borane-dimethylsulfide complex (1.98 ml, 20.2 mmol) in THF (18.3 ml), a 1M THF solution of 2,3-dimethyl-2-butene (20.2 ml, 20.2 mmol) was added at 0° C., and the mixture was stirred at the same temperature. Two hours later, the reaction solution was cooled to -25° C., and a solution of 3-cyclopentenecarboxylic acid methyl ester (2.55 g, 20.2 mmol) in THF (20 ml) was dropwise added thereto. The mixture was stirred at the same temperature for 1.5 hours. Then, methanol (1.64 ml) was dropwise added thereto. The reaction temperature was raised to 0° C., and the mixture was stirred for one hour. The reaction solution was concentrated under reduced pressure, dried and then dissolved in THF (20 ml). Separately, a n-butyllithium/1.5M hexane solution (1.37 ml, 20.6 mmol) was added at 0° C. to a solution of propargyl tetrahydropyranyl ether (2.83 g, 20.2 mmol) in THF (20 l), and the mixture was stirred for one hour. This solution was dropwise added at 0° C. to the above THF solution (10 ml). Then, the reaction solution was cooled to -78° C., and a solution of iodine (5.13 g, 20.2 mmol) in THF (10 ml) was dropwise added thereto, and the mixture was stirred at the same temperature for one hour and at room temperature for two hours. A 2N sodium hydroxide aqueous solution (12.1 ml) and a 30% hydrogen peroxide aqueous solution (2.83 ml) were dropwise added thereto, and the mixture was stirred for 5 minutes, then diluted with ethyl acetate (150 ml) and washed with a saturated sodium thiosulfate aqueous solution (150 ml) and a saturated sodium chloride aqueous solution (150 ml). The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the above identified compound (2.56 g, 47.6%). The mixture was stirred at the same temperature for 1.5 hours The reaction temperature was raised to 0° C. the mixture was stirred for one hour The reaction solution was concentrated under reduced pressure dried dissolved in THF (20 ml) the mixture was stirred for one hour Then, the reaction solution was cooled to -78° C. the mixture was stirred at the same temperature for one hour and at room temperature for two hours the mixture was stirred for 5 minutes washed with a saturated sodium thiosulfate aqueous solution (150 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography to obtain the

反応条件: temp:-25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of a borane-dimethylsulfide complex (1.98 ml, 20.2 mmol) in THF (18.3 ml), a 1M THF solution of 2,3-dimethyl-2-butene (20.2 ml, 20.2 mmol) was added at 0° C., and the mixture was stirred at the same temperature. Two hours later, the reaction solution was cooled to -25° C., and a solution of 3-cyclopentenecarboxylic acid methyl ester (2.55 g, 20.2 mmol) in THF (20 ml) was dropwise added thereto. The mixture was stirred at the same temperature for 1.5 hours. Then, methanol (1.64 ml) was dropwise added thereto. The reaction temperature was raised to 0° C., and the mixture was stirred for one hour. The reaction solution was concentrated under reduced pressure, dried and then dissolved in THF (20 ml). Separately, a n-butyllithium/1.5M hexane solution (1.37 ml, 20.6 mmol) was added at 0° C. to a solution of propargyl tetrahydropyranyl ether (2.83 g, 20.2 mmol) in THF (20 l), and the mixture was stirred for one hour. This solution was dropwise added at 0° C. to the above THF solution (10 ml). Then, the reaction solution was cooled to -78° C., and a solution of iodine (5.13 g, 20.2 mmol) in THF (10 ml) was dropwise added thereto, and the mixture was stirred at the same temperature for one hour and at room temperature for two hours. A 2N sodium hydroxide aqueous solution (12.1 ml) and a 30% hydrogen peroxide aqueous solution (2.83 ml) were dropwise added thereto, and the mixture was stirred for 5 minutes, then diluted with ethyl acetate (150 ml) and washed with a saturated sodium thiosulfate aqueous solution (150 ml) and a saturated sodium chloride aqueous solution (150 ml). The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the above identified compound (2.56 g, 47.6%). The mixture was stirred at the same temperature for 1.5 hours The reaction temperature was raised to 0° C. the mixture was stirred for one hour The reaction solution was concentrated under reduced pressure dried dissolved in THF (20 ml) the mixture was stirred for one hour Then, the reaction solution was cooled to -78° C. the mixture was stirred at the same temperature for one hour and at room temperature for two hours the mixture was stirred for 5 minutes washed with a saturated sodium thiosulfate aqueous solution (150 ml) The organic layer was dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography to obtain the

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 solution of methyl-3-cyclopentene-1-carboxylate (6.1 g, 48.4 mmole) in toluene (150 mL) and EtOH (75 mL) was added paraformaldehyde (10.6 g, 242 mmole), N-hydroxybenzylamine hydrochloride (11.4 g, 72.6 mmole) and triethylamine (10.1 mL, 72.6 mmole). After 24 hours at 80° C., the reaction solution was concentrated under vacuum and redissolved in hexanes/EtOAc, 4:1 (200 mL) and filtered. The organic solution was concentrated and then purified on silica (hexanes/EtOAc, 4:1) to give the title compound (10.7 g, 85%) as a light yellow oil containing mixture of diastereoisomers in the ratio of 6 (trans) to 1 (cis): LC-MS (ES) m/e 262 (M+H)+. the reaction solution was concentrated under vacuum redissolved in hexanes/EtOAc 4:1 (200 mL) and filtered The organic solution was concentrated purified on silica (hexanes/EtOAc, 4:1)