2-(1,4-dioxaspiro[4.5]decan-8-yl)ethanol

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a mixture of lithium aluminium hydride (831 mg) and anhydrous tetrahydrofuran (70 ml) at 0° C. was added a solution of ethyl 1,4-dioxaspiro[4.5]decane-8-acetate of Example 90 (2) (5.0 g) in anhydrous tetrahydrofuran (30 ml). The mixture was gradually warmed to about 25° C., stirred for 3 hours, and then sodium fluoride, water and dichloromethane were added to the reaction mixture. The precipitate was filtrated off with Celite, the filtrated organic layer was dried over sodium sulfate. The solvent was removed in vacuo from the organic layer to give 4.18 g of 8-(2-hydroxyethyl)-1,4-dioxaspiro[4.5]decane. The precipitate was filtrated off with Celite the filtrated organic layer was dried over sodium sulfate The solvent was removed in vacuo from the organic layer

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

実験手順: 2-(1,4-Dioxaspiro[4.5]dec-8-yl)ethanol (2.70 g, 0.0145 mol) was dissolved in acetone (10.00 mL) and THF (10.00 mL) and 6.00 M HCl (6.00 mL) was added. The reaction was stirred at 25° C. for 16 hours, neutralized with NaHCO3 solution and was then extracted with ethyl acetate. The organic extracts were washed with water, and with saturated NaCl, then dried (MgSO4) and concentrated in vacuo. The crude product was used in the next reaction without further purification. 1H NMR(CDCl3): 3.75 (m, 2H), 2.36 (m, 4H), 1.20-2.13 (m, 7H). was then extracted with ethyl acetate The organic extracts were washed with water with saturated NaCl, then dried (MgSO4) concentrated in vacuo The crude product was used in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 1,4-dioxaspiro[4.5]dec-8-ylacetate (3.40 g, 0.0149 mol) prepared according to the procedure of Itagaki, Noriaki; Kimura, Mari; Sugahara, Tsutomu; Iwabuchi, Yoshiharu. (Organic Letters 2005; 7 (19); 4181-4183.) was dissolved in ether (30.00 mL) and the mixture was cooled to 0° C. To the reaction was added 1.00 M lithium tetrahydroaluminate in ether (15.0 mL) and the resulting mixture was stirred at 0° C. for 60 minutes and at 25° C. for 2 hours. The reaction was cooled and water (0.40 mL, 0.022 mol) was added, followed by 1.00 M sodium hydroxide (0.40 mL). To the reaction was then added ether (100.00 mL) and the solid that precipitated was filtered off. The filtrate was concentrated using a rotary evaporator to give the product. 1H NMR(CDCl3): 3.94 (s, 4H), 3.67 (t, 2H), 1.20-1.80 (m, 11H). The reaction was cooled added ether (100.00 mL) and the solid that precipitated was filtered off The filtrate was concentrated a rotary evaporator to give the product

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

実験手順: 2-(1,4-Dioxaspiro[4.5]dec-8-yl)ethanol (2.70 g, 0.0145 mol) was dissolved in acetone (10.00 mL) and THF (10.00 mL) and 6.00 M HCl (6.00 mL) was added. The reaction was stirred at 25° C. for 16 hours, neutralized with NaHCO3 solution and was then extracted with ethyl acetate. The organic extracts were washed with water, and with saturated NaCl, then dried (MgSO4) and concentrated in vacuo. The crude product was used in the next reaction without further purification. 1H NMR (CDCl3): 3.75 (m, 2H), 2.36 (m, 4H), 1.20-2.13 (m, 7H). was then extracted with ethyl acetate The organic extracts were washed with water with saturated NaCl, then dried (MgSO4) concentrated in vacuo The crude product was used in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 1,4-dioxaspiro[4.5]dec-8-ylacetate (3.40 g, 0.0149 mol) prepared according to the procedure of Itagaki, Noriaki; Kimura, Mari; Sugahara, Tsutomu; Iwabuchi, Yoshiharu. (Organic Letters 2005; 7(19); 4181-4183.) was dissolved in ether (30.00 mL) and the mixture was cooled to 0° C. To the reaction was added 1.00 M lithium tetrahydroaluminate in ether (15.0 mL) and the resulting mixture was stirred at 0° C. for 60 minutes and at 25° C. for 2 hours. The reaction was cooled and water (0.40 mL, 0.022 mol) was added, followed by 1.00 M sodium hydroxide (0.40 mL). To the reaction was then added ether (100.00 mL) and the solid that precipitated was filtered off. The filtrate was concentrated using a rotary evaporator to give the product. 1H NMR (CDCl3): 3.94 (s, 4H), 3.67 (t, 2H), 1.20-1.80 (m, 11H). The reaction was cooled added ether (100.00 mL) and the solid that precipitated was filtered off The filtrate was concentrated a rotary evaporator to give the product

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: 2-(1,4-Dioxaspiro[4.5]dec-8-yl)ethanol (2.70 g, 0.0145 mol) was dissolved in acetone (10.00 mL) and THF (10.00 mL) and 6.00 M HCl (6.00 mL) was added. The reaction was stirred at 25° C. for 16 hours, neutralized with NaHCO3 solution and was then extracted with ethyl acetate. The organic extracts were washed with water, and with saturated NaCl, then dried (MgSO4) and concentrated in vacuo. The crude product was used in the next reaction without further purification. 1H NMR(CDCl3): 3.75 (m, 2H), 2.36 (m, 4H), 1.20-2.13 (m, 7H). was then extracted with ethyl acetate The organic extracts were washed with water with saturated NaCl, then dried (MgSO4) concentrated in vacuo The crude product was used in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 1,4-dioxaspiro[4.5]dec-8-ylacetate (3.40 g, 0.0149 mol) prepared according to the procedure of Itagaki, Noriaki; Kimura, Mari; Sugahara, Tsutomu; Iwabuchi, Yoshiharu. (Organic Letters 2005; 7 (19); 4181-4183.) was dissolved in ether (30.00 mL) and the mixture was cooled to 0° C. To the reaction was added 1.00 M lithium tetrahydroaluminate in ether (15.0 mL) and the resulting mixture was stirred at 0° C. for 60 minutes and at 25° C. for 2 hours. The reaction was cooled and water (0.40 mL, 0.022 mol) was added, followed by 1.00 M sodium hydroxide (0.40 mL). To the reaction was then added ether (100.00 mL) and the solid that precipitated was filtered off. The filtrate was concentrated using a rotary evaporator to give the product. 1H NMR(CDCl3): 3.94 (s, 4H), 3.67 (t, 2H), 1.20-1.80 (m, 11H). The reaction was cooled added ether (100.00 mL) and the solid that precipitated was filtered off The filtrate was concentrated a rotary evaporator to give the product

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

実験手順: 2-(1,4-Dioxaspiro[4.5]dec-8-yl)ethanol (2.70 g, 0.0145 mol) was dissolved in acetone (10.00 mL) and THF (10.00 mL) and 6.00 M HCl (6.00 mL) was added. The reaction was stirred at 25° C. for 16 hours, neutralized with NaHCO3 solution and was then extracted with ethyl acetate. The organic extracts were washed with water, and with saturated NaCl, then dried (MgSO4) and concentrated in vacuo. The crude product was used in the next reaction without further purification. 1H NMR (CDCl3): 3.75 (m, 2H), 2.36 (m, 4H), 1.20-2.13 (m, 7H). was then extracted with ethyl acetate The organic extracts were washed with water with saturated NaCl, then dried (MgSO4) concentrated in vacuo The crude product was used in the next reaction without further purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Ethyl 1,4-dioxaspiro[4.5]dec-8-ylacetate (3.40 g, 0.0149 mol) prepared according to the procedure of Itagaki, Noriaki; Kimura, Mari; Sugahara, Tsutomu; Iwabuchi, Yoshiharu. (Organic Letters 2005; 7(19); 4181-4183.) was dissolved in ether (30.00 mL) and the mixture was cooled to 0° C. To the reaction was added 1.00 M lithium tetrahydroaluminate in ether (15.0 mL) and the resulting mixture was stirred at 0° C. for 60 minutes and at 25° C. for 2 hours. The reaction was cooled and water (0.40 mL, 0.022 mol) was added, followed by 1.00 M sodium hydroxide (0.40 mL). To the reaction was then added ether (100.00 mL) and the solid that precipitated was filtered off. The filtrate was concentrated using a rotary evaporator to give the product. 1H NMR (CDCl3): 3.94 (s, 4H), 3.67 (t, 2H), 1.20-1.80 (m, 11H). The reaction was cooled added ether (100.00 mL) and the solid that precipitated was filtered off The filtrate was concentrated a rotary evaporator to give the product

反応条件: temp:3.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Fourth Step: 150.0 g of the compound (13), 274.3 g of triphenylphosphine (Ph3P), 71.3 g of imidazole and 900 mL of toluene were added to a reactor under nitrogen atmosphere, and stirred at 3° C. 255.5 g of iodine was added thereto by dividing into 10 portions at a temperature range of from 3 to 10° C., followed by further stirring at 0° C. for 3 hours. After confirming that the reaction had been completed by GC analysis, a yellow solid thus deposited was filtered off. The filtrate was concentrated, and 400 mL of heptane was added to the resulting residue, followed by filtering off a pale yellow solid thus deposited. The filtrate was concentrated, and the resulting residue was purified by silica gel column chromatography using toluene as eluent, and the solvent was removed by distillation under reduced pressure to obtain 223.9 g of 8-(2-iodoethyl)-1,4-dioxaspiro[4,5]decane (14) as a colorless transparent liquid. by dividing into 10 portions at a temperature range of from 3 to 10° C. by further stirring at 0° C. for 3 hours a yellow solid thus deposited was filtered off The filtrate was concentrated 400 mL of heptane was added to the resulting residue by filtering off a pale yellow solid The filtrate was concentrated the resulting residue was purified by silica gel column chromatography the solvent was removed by distillation under reduced pressure