(1S)-1-phenylpropane-1,3-diol

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

Procedure: Determination of the absolute configuration, optical purity and reaction yield of 1-phenyl-1,3-propanediol or a derivative thereof in the examples was determined by high pressure liquid chromatography (column: Chiral Cell OB, manufactured by Daisel Chemical Co., eluent: hexane/2-propanol (8/2), flow rate: 0.7 ml/min, detection: UV 210 nm). The reaction yield represents the mole percentage of (S)-1-phenyl-1,3-propanediol produced per mole of 1-phenylpropan-3-ol-1-one added as starting material. The reaction yield

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

Procedure: Determination of the absolute configuration, optical purity and reaction yield of 1-phenyl-1,3-propanediol or a derivative thereof in the examples was determined by high pressure liquid chromatography (column: Chiral Cell OB, manufactured by Daisel Chemical Co., eluent: hexane/2-propanol (8/2), flow rate: 0.7 ml/min, detection: UV 210 nm). The reaction yield represents the mole percentage of (S)-1-phenyl-1,3-propanediol produced per mole of 1-phenylpropan-3-ol-1-one added as starting material. The reaction yield

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Accordingly, the compound of Formula 37-1 (N-(2,4-dimethoxybenzyl)-3-[(1R)-3-hydroxy-1-phenylpropyl]-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide) was prepared from a solution provided by dissolving 200 mg of the compound of Formula 1-5 (0.429 mmol, prepared as described above) and (S)-1-phenylpropane-1,3-diol (65.3 mg, 0.429 mmol) (0.429 mmol) in 2 mL of THF. This solution was cooled to 0° C. and treated with triphenylphosphine (0.225 g, 0.858 mmol) followed by DEAD (0.136 mL, 0.858 mmol). After stirring at 0° C. for 120 min, the reaction mixture was diluted with EtOAc (50 mL) and saturated sodium bicarbonate (5 mL). The organic layer was washed with brine (10 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by normal phase chromatography (10-80% EtOAc in hexane) yielded the compound of Formula 37-1 as a yellow oil which was used as isolated. Accordingly, the compound of Formula 37-1 (N-(2,4-dimethoxybenzyl)-3-[(1R)-3-hydroxy-1-phenylpropyl]-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydro-1,3-benzoxazole-6-sulfonamide) was prepared from a solution provided The organic layer was washed with brine (10 mL) dried over sodium sulfate filtered concentrated in vacuo Purification by normal phase chromatography (10-80% EtOAc in hexane)

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

Procedure: To a solution of (S)-1-phenyl-propane-1,3-diol (0.5 g, 3.3 mmol) and triethylenediamine (368 mg, 3.3 mmol) in DCM (40 mL) cooled to 0° C. was added dropwise p-toluenesulfonyl chloride (1.96 g, 0.0103 mol) in DCM (20 mL). The reaction mixture was stirred for 1 h and then filtered through a pad of silica. The silica was washed with DCM and the filtrate was concentrated to give the title compound as a crude oil (0.485 mg). filtered through a pad of silica The silica was washed with DCM the filtrate was concentrated

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

Procedure: To a solution of (S)-1-phenyl-propane-1,3-diol (0.5 g, 3.3 mmol) and triethylenediamine (368 mg, 3.3 mmol) in DCM (40 mL) cooled to 0° C. was added dropwise p-toluenesulfonyl chloride (1.96 g, 0.0103 mol) in DCM (20 mL). The reaction mixture was stirred for 1 h and then filtered through a pad of silica. The silica was washed with DCM and the filtrate was concentrated to give the title compound as a crude oil (0.485 mg). filtered through a pad of silica The silica was washed with DCM the filtrate was concentrated

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

Procedure: Determination of the absolute configuration, optical purity and reaction yield of 1-phenyl-1,3-propanediol or a derivative thereof in the examples was determined by high pressure liquid chromatography (column: Chiral Cell OB, manufactured by Daisel Chemical Co., eluent: hexane/2-propanol (8/2), flow rate: 0.7 ml/min, detection: UV 210 nm). The reaction yield represents the mole percentage of (S)-1-phenyl-1,3-propanediol produced per mole of 1-phenylpropan-3-ol-1-one added as starting material. The reaction yield

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-1-phenyl-1,3-propanediol (125 g, 0.822 mole) in methyl tert-butyl ether (500 mL) was added triethylamine (135 mL). The reaction mixture was cooled to 0° C. and a solution of 4-bromobenzenesulfonyl chloride (230 g, 0.92 mole) in methyl tert-butyl ether (300 mL) and tetrahydrofuran (300 mL) was added dropwise over 3 hour. After the addition, the reaction mixture was stirred at 0° C. for three hours and was then warmed to ambient temperature. After stirring at ambient temperature for 18 hours, benzyltriethylammonium chloride (210 g, 0.92 mole) was added and the resulting mixture was heated at 55° C. for three hours. The reaction mixture was cooled to ambient temperature and then diluted with water. After separation of the organic phase, the aqueous phase was extracted two times with diethyl ether. The combined organic extracts were washed with 1.0 N hydrochloric acid, saturated aqueous sodium bicarbonate, water, saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure to provide an off-white solid (160 g). This solid was subjected to silica gel chromatography, eluting with ethyl acetate/hexane (1:9) to provide 110 grams (80%) of the title compound. After the addition was then warmed to ambient temperature After stirring at ambient temperature for 18 hours the resulting mixture was heated at 55° C. for three hours The reaction mixture was cooled to ambient temperature After separation of the organic phase the aqueous phase was extracted two times with diethyl ether The combined organic extracts were washed with 1.0 N hydrochloric acid, saturated aqueous sodium bicarbonate, water, saturated aqueous sodium chloride dried over magnesium sulfate concentrated under reduced pressure

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

Procedure: To a solution of (S)-1-phenyl-1,3-propanediol (8.0 g, 52.6 mmol) in dichloromethane (80 ml) were added at 0° C. acetic anhydride (5.5 ml) and pyridine (4.7 ml). The mixture was stirred for 6 hours at the same temperature range and for 1.5 hour at room temperature. The reaction mixture was washed with an aqueous solution of sodium hydrogencarbonate, water and a saturated aqueous saline solution, successively. The solvent was distilled off under reduced pressure. The residue was subjected to a silica gel column chromatography to give 4.8 g of (S)-3-hydroxy-3-phenylpropyl acetate. Physico-chemical properties and spectral data of these products are shown in [Table 7]. The reaction mixture was washed with an aqueous solution of sodium hydrogencarbonate, water The solvent was distilled off under reduced pressure

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of (S)-1-phenyl-1,3-propanediol (125 g, 0.822 mole) in methyl tert-butyl ether (500 mL) was added triethylamine (135 mL). The reaction mixture was cooled to 0° C. and a solution of 4-bromobenzenesulfonyl chloride (230 g, 0.92 mole) in methyl tert-butyl ether (300 mL) and tetrahydrofuran (300 mL) was added dropwise over 3 hour. After the addition, the reaction mixture was stirred at 0° C. for three hours and was then warmed to ambient temperature. After stirring at ambient temperature for 18 hours, benzyltriethylammonium chloride (210 g, 0.92 mole) was added and the resulting mixture was heated at 55° C. for three hours. The reaction mixture was cooled to ambient temperature and then diluted with water. After separation of the organic phase, the aqueous phase was extracted two times with diethyl ether. The combined organic extracts were washed with 1.0 N hydrochloric acid, saturated aqueous sodium bicarbonate, water, saturated aqueous sodium chloride, dried over magnesium sulfate, and concentrated under reduced pressure to provide an off-white solid (160 g). This solid was subjected to silica gel chromatography, eluting with ethyl acetate/hexane (1:9) to provide 110 grams (80%) of the title compound. After the addition was then warmed to ambient temperature After stirring at ambient temperature for 18 hours the resulting mixture was heated at 55° C. for three hours The reaction mixture was cooled to ambient temperature After separation of the organic phase the aqueous phase was extracted two times with diethyl ether The combined organic extracts were washed with 1.0 N hydrochloric acid, saturated aqueous sodium bicarbonate, water, saturated aqueous sodium chloride dried over magnesium sulfate concentrated under reduced pressure

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

Procedure: To a solution of (S)-1-phenyl-1,3-propanediol (8.0 g, 52.6 mmol) in dichloromethane (80 ml) were added at 0° C. acetic anhydride (5.5 ml) and pyridine (4.7 ml). The mixture was stirred for 6 hours at the same temperature range and for 1.5 hour at room temperature. The reaction mixture was washed with an aqueous solution of sodium hydrogencarbonate, water and a saturated aqueous saline solution, successively. The solvent was distilled off under reduced pressure. The residue was subjected to a silica gel column chromatography to give 4.8 g of (S)-3-hydroxy-3-phenylpropyl acetate. Physico-chemical properties and spectral data of these products are shown in [Table 7]. The reaction mixture was washed with an aqueous solution of sodium hydrogencarbonate, water The solvent was distilled off under reduced pressure

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 200 ml stainless steel-made autoclave were charged 426.5 mg of [RuI(p-cymene)(R)-Tol-BINAP]I3 prepared in Example 2, the diisopropyl ether solution of 3-phenyl-3-oxopropanal prepared in Reference Example 2, 100 ml of methanol, and 2.0 ml of degassed purified water in a nitrogen atmosphere, followed by stirring the mixture at 50° C. for 22 hours under a hydrogen pressure of 50 atm. The reaction mixture was concentrated and subjected to silica gel column chromatography (eluent: hexane/isopropanol=9/1 by volume) to eliminate the complex. The obtained hydrogenation product was dissolved in a 6-fold amount of diisopropyl ether by heating and allowed to stand at 0° C. for 24 hours. The resulting precipitate was collected by filtration and dried (room temperature, 1 mmHg), and 10.5 g of (1S)-phenyl-1,3-propanediol was obtained as a colorless crystal (percent yield: 45%). of degassed purified water in a nitrogen atmosphere The reaction mixture was concentrated The obtained hydrogenation product was dissolved in a 6-fold amount of diisopropyl ether by heating to stand at 0° C. for 24 hours The resulting precipitate was collected by filtration dried (room temperature, 1 mmHg)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 500 ml stainless steel-made autoclave were charged 65 g (400 mmole) of 3-phenyl-3-oxopropanol and 550 mg (0.4 mmole) of [RuI(p-cymene)((R)-BINAP)]I3 synthesized in Example 1 in a nitrogen atmosphere, and 300 ml of methanol was added thereto, followed by stirring the mixture at 30° C. for 20 hours under a hydrogen pressure of 30 atm. The reaction mixture was concentrated and subjected to silica gel column chromatography (eluent: hexane/isopropanol=9/1 by volume) to eliminate the complex. The obtained hydrogenation product was dissolved in a 6-fold amount of diisopropyl ether by heating and allowed to stand at 0° C. for 24 hours. The resulting precipitate was collected by filtration and dried (room temperature, 1 mmHg), and 45.5 g of (1S)-phenyl-1,3-propanediol was obtained as a colorless crystal (percent yield: 70.0%). was added The reaction mixture was concentrated The obtained hydrogenation product was dissolved in a 6-fold amount of diisopropyl ether by heating to stand at 0° C. for 24 hours The resulting precipitate was collected by filtration dried (room temperature, 1 mmHg)