(2R)-2-hexyloxirane

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

Procedure: Under nitrogen atmosphere, 10 g (65.5 mM) of (R)-1,2-epoxyoctane and 100 ml of dry diethyl ether (Et2O) were placed in a 200 ml two-necked round-bottomed flask and cooled on an ice bath. Into the mixture, hydrogen chloride gas was blown, followed by stirring for 2.5 hours. Then, the ice bath was removed and the mixture was further stirred for 2 hours at room temperature. After the reaction, the reaction mixture was poured into 250 ml of ice water and subjected to extraction with diethyl ether. The organic layer was washed with distilled water and dried with anhydrous magnesium sulfate, followed by distilling-off of the solvent to obtain 10.4 g of (R)-1-chloro-2-octanol. cooled on an ice bath Then, the ice bath was removed the mixture was further stirred for 2 hours at room temperature After the reaction subjected to extraction with diethyl ether The organic layer was washed with distilled water dried with anhydrous magnesium sulfate

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

Procedure: To 30 ml of hydrogen fluoride pyridine solution which was cooled with ice, 8.5 g of (R)-1,2-epoxyoctane in 20 ml of ether was added dropwise. The mixture was stirred for one hour at the same temperature and brought to room temperature. 100 ml of water was added to the mixture. After extracting it with 50 ml of ether twice, the obtained organic layer was washed with an alkali solution and then with water, dried over magnesium sulfate and concentrated. The concentrate was distilled under reduced pressure and 4.9 g of distillate was obtained at 126°-129° C./80 mmHg. 3.7 g of (S)-2-fluorooctane-1-ol was obtained by recrystallization from 40 ml of heptane. Its melting point was 33°-35° C., [α]D26 -13.14 (c1.7, benzene) of optical rotation was shown. was added dropwise brought to room temperature After extracting it with 50 ml of ether twice the obtained organic layer was washed with an alkali solution with water, dried over magnesium sulfate concentrated The concentrate was distilled under reduced pressure and 4.9 g of distillate was obtained at 126°-129° C./80 mmHg

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

Procedure: To 30 ml of hydrogen fluoride pyridine solution which was cooled with ice, 8.5 g of (R)-1,2-epoxyoctane in 20 ml of ether was added dropwise. The mixture was stirred for one hour at the same temperature and brought to room temperature. 100 ml of water was added to the mixture. After extracting it with 50 ml of ether twice, the obtained organic layer was washed with an alkali solution and then with water, dried over magnesium sulfate and concentrated. The concentrate was distilled under reduced pressure and 4.9 g of distillate was obtained at 126°-129° C./80 mmHg. 3.7 g of (S)-2-fluorooctane-1-ol was obtained by recrystallization from 40 ml of heptane. Its melting point was 33°-35° C., [α]D26 -13.14 (c1.7, benzene) of optical rotation was shown. was added dropwise brought to room temperature After extracting it with 50 ml of ether twice the obtained organic layer was washed with an alkali solution with water, dried over magnesium sulfate concentrated The concentrate was distilled under reduced pressure and 4.9 g of distillate was obtained at 126°-129° C./80 mmHg

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

Procedure: To a solution of 1.02 g (4.6 mmol) of 4-(4-methoxyphenyl)phenylacetonitrile in 40 ml of tetrahydrofuran (THF) was added, at -78° C., 1.5 M n-BuLi solution in hexane in an amount of 3.6 ml (5.5 mmol). This mixture was stirred for 1 hour. Thereto were added a solution of 705 mg (5.5 mmol) of (R)-1,2-epoxyoctane in 20 ml of THF and 5 ml of HMPA. The resulting mixture was warmed to room temperature, and then stirred overnight. The reaction mixture was neutralized with 3 M hydrochloric acid, and then subjected to extraction with 300 ml of ethyl acetate. The resulting ethyl acetate solution was washed with saturated sodium chloride aqueous solution, dried with anhydrous magnesium sulfate, filtered, and then concentrated. The residue was separated and purified by column chromatography (hexane/ethyl acetate=3/1), thereby obtaining 1.05 g (yield 65%) of (4R)-4-hydroxy-2-[4-(4-methoxyphenyl)phenyl]decanenitrile. stirred overnight subjected to extraction with 300 ml of ethyl acetate The resulting ethyl acetate solution was washed with saturated sodium chloride aqueous solution dried with anhydrous magnesium sulfate filtered concentrated The residue was separated purified by column chromatography (hexane/ethyl acetate=3/1)

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

Procedure: To a solution of 1.02 g (4.6 mmol) of 4-(4-methoxyphenyl)phenylacetonitrile in 40 ml of tetrahydrofuran (THF) was added, at -78° C., 1.5 M n-BuLi solution in hexane in an amount of 3.6 ml (5.5 mmol). This mixture was stirred for 1 hour. Thereto were added a solution of 705 mg (5.5 mmol) of (R)-1,2-epoxyoctane in 20 ml of THF and 5 ml of HMPA. The resulting mixture was warmed to room temperature, and then stirred overnight. The reaction mixture was neutralized with 3 M hydrochloric acid, and then subjected to extraction with 300 ml of ethyl acetate. The resulting ethyl acetate solution was washed with saturated sodium chloride aqueous solution, dried with anhydrous magnesium sulfate, filtered, and then concentrated. The residue was separated and purified by column chromatography (hexane/ethyl acetate=3/1), thereby obtaining 1.05 g (yield 65%) of (4R)-4-hydroxy-2-[4-(4-methoxyphenyl)phenyl]decanenitrile. stirred overnight subjected to extraction with 300 ml of ethyl acetate The resulting ethyl acetate solution was washed with saturated sodium chloride aqueous solution dried with anhydrous magnesium sulfate filtered concentrated The residue was separated purified by column chromatography (hexane/ethyl acetate=3/1)

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-Hexyloxirane (1.22 mL, 100% ee) was added dropwise to a tetrahydrofuran (2.21 mL) solution of copper chloride (15.8 mg) at −20° C. under argon atmosphere, and then a 2.11 mol/L ethyl magnesium chloride in tetrahydrofuran solution (4.55 mL) was added dropwise thereto. The reaction mixture was stirred at −20° C. for 1.5 hours, and a tetrahydrofuran solution of p-toluenesulfonyl chloride (1.83 g) was added dropwise thereto, followed by stirring for 1.5 hours. Then, the temperature was raised up to 0° C., followed by stirring for 3.5 hours. To the reaction solution were added water and pyridine, followed by stirring at 0° C. for 40 minutes, ethyl acetate was added thereto and the mixture was successively washed with 10% sulfuric acid (twice), water and brine and concentrated to give the title compound (2.27 g) having the following physical data. by stirring for 1.5 hours Then, the temperature was raised up to 0° C. by stirring for 3.5 hours by stirring at 0° C. for 40 minutes the mixture was successively washed with 10% sulfuric acid (twice), water and brine concentrated

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (2R)-2-Hexyloxirane (1.22 mL, 100% ee) was added dropwise to a tetrahydrofuran (2.21 mL) solution of copper chloride (15.8 mg) at −20° C. under argon atmosphere, and then a 2.11 mol/L ethyl magnesium chloride in tetrahydrofuran solution (4.55 mL) was added dropwise thereto. The reaction mixture was stirred at −20° C. for 1.5 hours, and a tetrahydrofuran solution of p-toluenesulfonyl chloride (1.83 g) was added dropwise thereto, followed by stirring for 1.5 hours. Then, the temperature was raised up to 0° C., followed by stirring for 3.5 hours. To the reaction solution were added water and pyridine, followed by stirring at 0° C. for 40 minutes, ethyl acetate was added thereto and the mixture was successively washed with 10% sulfuric acid (twice), water and brine and concentrated to give the title compound (2.27 g) having the following physical data. by stirring for 1.5 hours Then, the temperature was raised up to 0° C. by stirring for 3.5 hours by stirring at 0° C. for 40 minutes the mixture was successively washed with 10% sulfuric acid (twice), water and brine concentrated

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

Procedure: Under nitrogen atmosphere, 10 g (65.5 mM) of (R)-1,2-epoxyoctane and 100 ml of dry diethyl ether (Et2O) were placed in a 200 ml two-necked round-bottomed flask and cooled on an ice bath. Into the mixture, hydrogen chloride gas was blown, followed by stirring for 2.5 hours. Then, the ice bath was removed and the mixture was further stirred for 2 hours at room temperature. After the reaction, the reaction mixture was poured into 250 ml of ice water and subjected to extraction with diethyl ether. The organic layer was washed with distilled water and dried with anhydrous magnesium sulfate, followed by distilling-off of the solvent to obtain 10.4 g of (R)-1-chloro-2-octanol. cooled on an ice bath Then, the ice bath was removed the mixture was further stirred for 2 hours at room temperature After the reaction subjected to extraction with diethyl ether The organic layer was washed with distilled water dried with anhydrous magnesium sulfate

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

Procedure: Under an argon atmosphere, cuprous chloride (4.6 g) was added to a solution of (2R)-2-hexyloxirane (300 g) in tetrahydrofuran (642 mL), and then ethylmagnesium chloride tetrahydrofuran solution (2.1 mol/L, 1309 g) was added dropwise at −40 to −20° C. (inner temperature). The reaction mixture was stirred at −30 to −20° C. (inner temperature) for about 30 minutes, and then tosyl chloride (491 g) was added, and the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours. To the reaction mixture was then added 10 v/v % sulfuric acid (conc. sulfuric acid:water=65 mL:650 mL), aqueous sodium chloride (13.6 g) solution (272 mL) and ethyl acetate (1.5 L) for extraction. The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) and a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated to give the title compound (758.7 g; yield 89%). the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours for extraction The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated

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

Procedure: Under an argon atmosphere, cuprous chloride (4.6 g) was added to a solution of (2R)-2-hexyloxirane (300 g) in tetrahydrofuran (642 mL), and then ethylmagnesium chloride tetrahydrofuran solution (2.1 mol/L, 1309 g) was added dropwise at −40 to −20° C. (inner temperature). The reaction mixture was stirred at −30 to −20° C. (inner temperature) for about 30 minutes, and then tosyl chloride (491 g) was added, and the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours. To the reaction mixture was then added 10 v/v % sulfuric acid (conc. sulfuric acid:water=65 mL:650 mL), aqueous sodium chloride (13.6 g) solution (272 mL) and ethyl acetate (1.5 L) for extraction. The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) and a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated to give the title compound (758.7 g; yield 89%). the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours for extraction The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated

Conditions: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Butylphenylacetic acid (5 g) was dissolved in THF (100 ml), followed by cooling the solution down to -60° C., dropwise adding a tetrahydrofuran solution of LDA (10.4 mmol) over 30 minutes, raising the temperature up to 0° C., agitating for 30 minutes, cooling down to -60° C., dropwise adding a mixed solution of (R)-1,2-epoxyoctane (3.4 g) with anhydrous THF (5 ml) over 10 minutes, gradually raising the temperature, agitating at room temperature overnight, pouring the reaction solution in ice water (100 ml) and toluene (200 ml), washing the resulting organic layer with 6N--HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over anhydrous magnesium sulfate, concentrating the organic layer under reduced pressure, placing the resulting concentrate in a 1 l three-necked flask, adding toluene (250 ml) and p-toluenesulfonic acid (1.1 g), heating the mixture under reflux for 4 hours, dehydrating with a Dien-Stark type drain tube, adding ice water (100 ml), washing the organic layer with 6N--HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over magnesium sulfate, concentrating the organic layer under reduced pressure, separation-purifying according to chromatography and recrystallizing from ethanol to obtain (αS,γR)-α-(4-butylphenyl)-γ-hexyl-γ-butyrolactone (trans-form) (0.8 g). m.p.: 37.7° C. raising the temperature up to 0° C. cooling down to -60° C. gradually raising the temperature agitating at room temperature overnight toluene (200 ml), washing the resulting organic layer with 6N HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over anhydrous magnesium sulfate concentrating the organic layer under reduced pressure concentrate in a 1 l three-necked flask adding toluene (250 ml) and p-toluenesulfonic acid (1.1 g) heating the mixture under reflux for 4 hours adding ice water (100 ml) washing the organic layer with 6N HCl, 2N--NaOH and saturated NaCl aqueous solution in this order, drying over magnesium sulfate concentrating the organic layer under reduced pressure separation-purifying recrystallizing from ethanol

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

Procedure: Under an argon atmosphere, cuprous chloride (4.6 g) was added to a solution of (2R)-2-hexyloxirane (300 g) in tetrahydrofuran (642 mL), and then ethylmagnesium chloride tetrahydrofuran solution (2.1 mol/L, 1309 g) was added dropwise at −40 to −20° C. (inner temperature). The reaction mixture was stirred at −30 to −20° C. (inner temperature) for about 30 minutes, and then tosyl chloride (491 g) was added, and the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours. To the reaction mixture was then added 10 v/v % sulfuric acid (conc. sulfuric acid:water=65 mL:650 mL), aqueous sodium chloride (13.6 g) solution (272 mL) and ethyl acetate (1.5 L) for extraction. The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) and a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated to give the title compound (758.7 g; yield 89%). the mixture was stirred at 0-20° C. (inner temperature) for about 4 hours for extraction The resulting organic layer was washed with (1) a solution of sodium chloride (32 g) in water (636 mL), (2) a mixture of a solution of potassium carbonate (73 g) in water (730 mg) a saturated brine (200 mL), and (3) a saturated brine (600 mL) in order, and then concentrated