tert-butyl N-[(1S)-1-(3-fluorophenyl)-2-hydroxyethyl]carbamate

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

Procedure: To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%). via addition funnel The reaction was then concentrated was added The resulting suspension was then filtered through Celite the solids were washed with additional ethyl acetate The filtrate was then concentrated to a sticky solid dried under high vacuum briefly The resulting residue was dissolved in acetonitrile (25 mL) the mixture was extracted with ethyl acetate three times The combined organics were dried over sodium sulfate concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)

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

Procedure: To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%). via addition funnel The reaction was then concentrated was added The resulting suspension was then filtered through Celite the solids were washed with additional ethyl acetate The filtrate was then concentrated to a sticky solid dried under high vacuum briefly The resulting residue was dissolved in acetonitrile (25 mL) the mixture was extracted with ethyl acetate three times The combined organics were dried over sodium sulfate concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)

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

Procedure: To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%). via addition funnel The reaction was then concentrated was added The resulting suspension was then filtered through Celite the solids were washed with additional ethyl acetate The filtrate was then concentrated to a sticky solid dried under high vacuum briefly The resulting residue was dissolved in acetonitrile (25 mL) the mixture was extracted with ethyl acetate three times The combined organics were dried over sodium sulfate concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Tert-butyl (S)-1-(3-fluorophenyl)-2-hydroxyethylcarbamate (256 mg, 1.0 mmol) was dissolved in acetonitrile (10 mL) and treated with cesium carbonate (391 mg, 1.2 mmol) and ethyl bromoacetate (0.14 mL, 1.25 mmol). The mixture was heated to 100° C. for 30 min, then cooled to room temperature, acidified, and extracted with ethyl acetate. Purification on silica gel (15%-40% ethyl acetate/hexanes) gave 69 mg of tert-butyl (S)-2-((ethoxycarbonyl)methoxy)-1-(3-fluorophenyl)ethylcarbamate as a colorless glass. HPLC-MS calculated for C17H24FNO5 (M+H+) 342.2, found 342.1. cooled to room temperature extracted with ethyl acetate Purification on silica gel (15%-40% ethyl acetate/hexanes)

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

Procedure: To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%). via addition funnel The reaction was then concentrated was added The resulting suspension was then filtered through Celite the solids were washed with additional ethyl acetate The filtrate was then concentrated to a sticky solid dried under high vacuum briefly The resulting residue was dissolved in acetonitrile (25 mL) the mixture was extracted with ethyl acetate three times The combined organics were dried over sodium sulfate concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)

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

Procedure: To a solution of thionyl chloride (1.64 mL, 22.5 mmol) in acetonitrile (40 mL) at −40° C. was added dropwise a solution of the [(S)-1-(3-Fluoro-phenyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (2.30 g, 9.0 mmol) in acetonitrile (100 mL) via addition funnel. Pyridine (3.64 mL, 45.0 mmol) was then added dropwise and the reaction was warmed to room temperature for 2 hours. The reaction was then concentrated to ¼ volume in vacuo and 350-400 mL of ethyl acetate was added. The resulting suspension was then filtered through Celite and the solids were washed with additional ethyl acetate. The filtrate was then concentrated to a sticky solid and dried under high vacuum briefly. The resulting residue was dissolved in acetonitrile (25 mL) and RuCl3—H2O (219 mg, 0.9 mmol) was added followed by sodium periodate (2.31 g, 10.8 mmol) and water (25 mL). The dark solution was stirred for 4 hours at which time it was diluted with ethyl acetate (100 mL) and water (100 mL) and the mixture was extracted with ethyl acetate three times. The combined organics were dried over sodium sulfate and concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane) to provide the product as a white solid (2.47 g, 86.4%). via addition funnel The reaction was then concentrated was added The resulting suspension was then filtered through Celite the solids were washed with additional ethyl acetate The filtrate was then concentrated to a sticky solid dried under high vacuum briefly The resulting residue was dissolved in acetonitrile (25 mL) the mixture was extracted with ethyl acetate three times The combined organics were dried over sodium sulfate concentrated to a residue that was purified by column chromatography (5% ethyl acetate/heptane to 75% ethyl acetate/heptane)