(1R)-1-(3-chlorophenyl)ethane-1,2-diol

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

Procedure: At about 0° C., trimethylsilyl chloride (3.7 g, 34.06 mmol, 1.5 equiv.) was added to a solution of (R)-1-(3-chlorophenyl)ethane-1,2-diol (4 g, 23.17 mmol, 1 equiv.) and triethyl orthoacetate (5.6 g, 34.52 mmol, 1.5 equiv.) in dichloromethane (20 mL). After stirring the solution for about 1 hour, the solvent was removed by evaporation. The resulting crude product was resuspended in dry methanol (20 mL) and then potassium carbonate (8 g, 57.88 mmol, 2.5 equiv.) was added. The suspension was stirred vigorously for about 2 hours, and then filtered. The resulting filtrate was washed with dichloromethane and then concentrated in vacuo. The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15)) to obtain the title product as a colorless oil (2.2 g; yield=61%). 1H NMR (300 MHz, DMSO-d6) δ: 7.25-7.43 (m, 4H), 3.97 (m, 1H), 3.13 (m, 1H), 2.88 (m, 1H). the solvent was removed by evaporation The suspension was stirred vigorously for about 2 hours filtered The resulting filtrate was washed with dichloromethane concentrated in vacuo The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15))

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

Procedure: At 0-5° C., sodium borohydride (2.3 g, 60.80 mmol, 2.50 equiv) was added in several batches to a solution of (R)-Methyl 2-(3-chlorophenyl)-2-hydroxyacetate (5 g, 24.92 mmol, 1.00 equiv.) in methanol (50 mL). The resulting solution was stirred at ambient temperature for about 2 hours, and then 10% ammonium chloride (20 mL) was added. The mixture was concentrated in vacuo, and extracted with ethyl acetate (3×50 mL). The organic layers were combined and concentrated in vacuo to give the title product as a colorless oil (4 g; yield=93%). 1H NMR (300 MHz, DMSO-d6) δ: 7.26-7.39 (m, 4H), 5.40 (d, J=1.5 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.54 (q, J=5.7 Hz, 1H), 3.48 (m, 2H). The mixture was concentrated in vacuo extracted with ethyl acetate (3×50 mL) concentrated in vacuo

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

Procedure: Into toluene (30 ml) were added (R)-2-(3-chlorophenyl)-2-hydroxyethanol obtained in 1) above (7 g), pyridine (8.0 g) and further, under ice-cooling and dropwise, p-toluenesulfonyl chloride (9.3 g), and then the resulting mixture was stirred at the same temperature for 24 hours. The solid thus precipitated was filtered off, the filtrate was concentrated, and the residue was dissolved in toluene (40 ml) and then washed with dilute hydrochloric acid. The organic layer was collected by layer separation, washed with a saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The desiccant was filtered off, the solvent was distilled off under reduced pressure, and the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound mentioned above (10.6 g, 80.0%). further, under ice-cooling The solid thus precipitated was filtered off the filtrate was concentrated the residue was dissolved in toluene (40 ml) washed with dilute hydrochloric acid The organic layer was collected by layer separation washed with a saturated aqueous sodium chloride solution dried with anhydrous magnesium sulfate The desiccant was filtered off the solvent was distilled off under reduced pressure the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound

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

Procedure: Into toluene (30 ml) were added (R)-2-(3-chlorophenyl)-2-hydroxyethanol obtained in 1) above (7 g), pyridine (8.0 g) and further, under ice-cooling and dropwise, p-toluenesulfonyl chloride (9.3 g), and then the resulting mixture was stirred at the same temperature for 24 hours. The solid thus precipitated was filtered off, the filtrate was concentrated, and the residue was dissolved in toluene (40 ml) and then washed with dilute hydrochloric acid. The organic layer was collected by layer separation, washed with a saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The desiccant was filtered off, the solvent was distilled off under reduced pressure, and the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound mentioned above (10.6 g, 80.0%). further, under ice-cooling The solid thus precipitated was filtered off the filtrate was concentrated the residue was dissolved in toluene (40 ml) washed with dilute hydrochloric acid The organic layer was collected by layer separation washed with a saturated aqueous sodium chloride solution dried with anhydrous magnesium sulfate The desiccant was filtered off the solvent was distilled off under reduced pressure the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound

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

Procedure: Into THF (70 ml) were added (R)-3-chloromandelic acid (10 g) and further, under ice-cooling and dropwise, a 1M-diborane THF solution (81.5 ml) over 2 hours, and then stirring was continued at 25° C. for 12 hours. The reaction mixture was cooled, methanol (20 ml) was added thereto over 30 minutes and then stirring was further continued for 3 hours. The resulting reaction mixture was concentrated and then the residue was recrystallized from diethyl ether to obtain a colorless oily compound mentioned above (7.3 g, 78.9%). further, under ice-cooling The reaction mixture was cooled over 30 minutes stirring was further continued for 3 hours The resulting reaction mixture was concentrated the residue was recrystallized from diethyl ether to obtain a colorless oily compound

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

Procedure: Into THF (70 ml) were added (R)-3-chloromandelic acid (10 g) and further, under ice-cooling and dropwise, a 1M-diborane THF solution (81.5 ml) over 2 hours, and then stirring was continued at 25° C. for 12 hours. The reaction mixture was cooled, methanol (20 ml) was added thereto over 30 minutes and then stirring was further continued for 3 hours. The resulting reaction mixture was concentrated and then the residue was recrystallized from diethyl ether to obtain a colorless oily compound mentioned above (7.3 g, 78.9%). further, under ice-cooling The reaction mixture was cooled over 30 minutes stirring was further continued for 3 hours The resulting reaction mixture was concentrated the residue was recrystallized from diethyl ether to obtain a colorless oily compound

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

Procedure: At about 0° C., trimethylsilyl chloride (3.7 g, 34.06 mmol, 1.5 equiv.) was added to a solution of (R)-1-(3-chlorophenyl)ethane-1,2-diol (4 g, 23.17 mmol, 1 equiv.) and triethyl orthoacetate (5.6 g, 34.52 mmol, 1.5 equiv.) in dichloromethane (20 mL). After stirring the solution for about 1 hour, the solvent was removed by evaporation. The resulting crude product was resuspended in dry methanol (20 mL) and then potassium carbonate (8 g, 57.88 mmol, 2.5 equiv.) was added. The suspension was stirred vigorously for about 2 hours, and then filtered. The resulting filtrate was washed with dichloromethane and then concentrated in vacuo. The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15)) to obtain the title product as a colorless oil (2.2 g; yield=61%). 1H NMR (300 MHz, DMSO-d6) δ: 7.25-7.43 (m, 4H), 3.97 (m, 1H), 3.13 (m, 1H), 2.88 (m, 1H). the solvent was removed by evaporation The suspension was stirred vigorously for about 2 hours filtered The resulting filtrate was washed with dichloromethane concentrated in vacuo The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15))

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

Procedure: At 0-5° C., sodium borohydride (2.3 g, 60.80 mmol, 2.50 equiv) was added in several batches to a solution of (R)-Methyl 2-(3-chlorophenyl)-2-hydroxyacetate (5 g, 24.92 mmol, 1.00 equiv.) in methanol (50 mL). The resulting solution was stirred at ambient temperature for about 2 hours, and then 10% ammonium chloride (20 mL) was added. The mixture was concentrated in vacuo, and extracted with ethyl acetate (3×50 mL). The organic layers were combined and concentrated in vacuo to give the title product as a colorless oil (4 g; yield=93%). 1H NMR (300 MHz, DMSO-d6) δ: 7.26-7.39 (m, 4H), 5.40 (d, J=1.5 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.54 (q, J=5.7 Hz, 1H), 3.48 (m, 2H). The mixture was concentrated in vacuo extracted with ethyl acetate (3×50 mL) concentrated in vacuo

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

Procedure: At about 0° C., trimethylsilyl chloride (3.7 g, 34.06 mmol, 1.5 equiv.) was added to a solution of (R)-1-(3-chlorophenyl)ethane-1,2-diol (4 g, 23.17 mmol, 1 equiv.) and triethyl orthoacetate (5.6 g, 34.52 mmol, 1.5 equiv.) in dichloromethane (20 mL). After stirring the solution for about 1 hour, the solvent was removed by evaporation. The resulting crude product was resuspended in dry methanol (20 mL) and then potassium carbonate (8 g, 57.88 mmol, 2.5 equiv.) was added. The suspension was stirred vigorously for about 2 hours, and then filtered. The resulting filtrate was washed with dichloromethane and then concentrated in vacuo. The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15)) to obtain the title product as a colorless oil (2.2 g; yield=61%). 1H NMR (300 MHz, DMSO-d6) δ: 7.25-7.43 (m, 4H), 3.97 (m, 1H), 3.13 (m, 1H), 2.88 (m, 1H). the solvent was removed by evaporation The suspension was stirred vigorously for about 2 hours filtered The resulting filtrate was washed with dichloromethane concentrated in vacuo The resulting crude was purified by silica gel column chromatography (ethyl acetate:petroleum ether (1:15))

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

Procedure: At 0-5° C., sodium borohydride (2.3 g, 60.80 mmol, 2.50 equiv) was added in several batches to a solution of (R)-Methyl 2-(3-chlorophenyl)-2-hydroxyacetate (5 g, 24.92 mmol, 1.00 equiv.) in methanol (50 mL). The resulting solution was stirred at ambient temperature for about 2 hours, and then 10% ammonium chloride (20 mL) was added. The mixture was concentrated in vacuo, and extracted with ethyl acetate (3×50 mL). The organic layers were combined and concentrated in vacuo to give the title product as a colorless oil (4 g; yield=93%). 1H NMR (300 MHz, DMSO-d6) δ: 7.26-7.39 (m, 4H), 5.40 (d, J=1.5 Hz, 1H), 4.77 (t, J=5.7 Hz, 1H), 4.54 (q, J=5.7 Hz, 1H), 3.48 (m, 2H). The mixture was concentrated in vacuo extracted with ethyl acetate (3×50 mL) concentrated in vacuo

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

Procedure: Into toluene (30 ml) were added (R)-2-(3-chlorophenyl)-2-hydroxyethanol obtained in 1) above (7 g), pyridine (8.0 g) and further, under ice-cooling and dropwise, p-toluenesulfonyl chloride (9.3 g), and then the resulting mixture was stirred at the same temperature for 24 hours. The solid thus precipitated was filtered off, the filtrate was concentrated, and the residue was dissolved in toluene (40 ml) and then washed with dilute hydrochloric acid. The organic layer was collected by layer separation, washed with a saturated aqueous sodium chloride solution and dried with anhydrous magnesium sulfate. The desiccant was filtered off, the solvent was distilled off under reduced pressure, and the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound mentioned above (10.6 g, 80.0%). further, under ice-cooling The solid thus precipitated was filtered off the filtrate was concentrated the residue was dissolved in toluene (40 ml) washed with dilute hydrochloric acid The organic layer was collected by layer separation washed with a saturated aqueous sodium chloride solution dried with anhydrous magnesium sulfate The desiccant was filtered off the solvent was distilled off under reduced pressure the residue was recrystallized from diethyl ether and hexane to obtain a colorless oily compound

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

Procedure: Into THF (70 ml) were added (R)-3-chloromandelic acid (10 g) and further, under ice-cooling and dropwise, a 1M-diborane THF solution (81.5 ml) over 2 hours, and then stirring was continued at 25° C. for 12 hours. The reaction mixture was cooled, methanol (20 ml) was added thereto over 30 minutes and then stirring was further continued for 3 hours. The resulting reaction mixture was concentrated and then the residue was recrystallized from diethyl ether to obtain a colorless oily compound mentioned above (7.3 g, 78.9%). further, under ice-cooling The reaction mixture was cooled over 30 minutes stirring was further continued for 3 hours The resulting reaction mixture was concentrated the residue was recrystallized from diethyl ether to obtain a colorless oily compound