(2S)-2-amino-2-cyclopropylethanol

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

実験手順: To a cold, stirred suspension of sodium hydride (600 mg, 14.99 mmol) in toluene (20 mL) was added dropwise a solution of (S)-2-amino-2-cyclopropylethanol (680 mg, 6.72 mmol)) in toluene (12 mL). The reaction mixture was then allowed to warm to room temperature and a solution of ethyl chloroacetate (824 mg, 6.72 mmol) in toluene (4 mL) was added dropwise. The resulting mixture was stirred for 3 h at room temperature. The mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid and concentrated under vacuum. The residue was diluted with THF, dried with magnesium sulfate, concentrated under vacuum and filtered through a pad of silica gel, flushing with additional THF. The resulting filtrate was concentrated under vacuum, and the residue was further purified by flash chromatography (ISCO, 12 g silica gel column, using a 0-100% ethyl acetate in n-heptane gradient as the eluent to afford 208 mg of (S)-5-cyclopropylmorpholin-3-one as a white solid (MS: (M+H)+=142.2). The resulting mixture was stirred for 3 h at room temperature The mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid concentrated under vacuum The residue was diluted with THF dried with magnesium sulfate concentrated under vacuum filtered through a pad of silica gel flushing with additional THF The resulting filtrate was concentrated under vacuum the residue was further purified by flash chromatography (ISCO, 12 g silica gel column

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

実験手順: To a cold, stirred suspension of sodium hydride (600 mg, 14.99 mmol) in toluene (20 mL) was added dropwise a solution of (S)-2-amino-2-cyclopropylethanol (680 mg, 6.72 mmol)) in toluene (12 mL). The reaction mixture was then allowed to warm to room temperature and a solution of ethyl chloroacetate (824 mg, 6.72 mmol) in toluene (4 mL) was added dropwise. The resulting mixture was stirred for 3 h at room temperature. The mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid and concentrated under vacuum. The residue was diluted with THF, dried with magnesium sulfate, concentrated under vacuum and filtered through a pad of silica gel, flushing with additional THF. The resulting filtrate was concentrated under vacuum, and the residue was further purified by flash chromatography (ISCO, 12 g silica gel column, using a 0-100% ethyl acetate in n-heptane gradient as the eluent to afford 208 mg of (S)-5-cyclopropylmorpholin-3-one as a white solid (MS: (M+H)+=142.2). The resulting mixture was stirred for 3 h at room temperature The mixture was then quenched with the addition of 10 mL of 1N aq. hydrochloric acid concentrated under vacuum The residue was diluted with THF dried with magnesium sulfate concentrated under vacuum filtered through a pad of silica gel flushing with additional THF The resulting filtrate was concentrated under vacuum the residue was further purified by flash chromatography (ISCO, 12 g silica gel column

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3S,5R,6R)-3-Allyl-6-(4-chloro-3-fluorophenyl)-5-(3-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one (32 g, 81 mmol, Example 4, Step E) was combined with (S)-2-amino-2-cyclopropylethanol (26.7 g, 265 mmol) and the suspension was heated at 100° C. overnight. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and washed with 1 N hydrochloric acid (2×), water, and brine. The organic layer was dried over magnesium sulfate and concentrated under vacuum to provide the title compound as a white solid. The reaction mixture was cooled to room temperature washed with 1 N hydrochloric acid (2×), water, and brine The organic layer was dried over magnesium sulfate concentrated under vacuum

反応条件: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3S,5R,6R)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyltetrahydro-2H-pyran-2-one (125.0 g, 333 mmol, Example 1, Step D) was added to (S)-2-amino-2-cyclopropylethanol (101 g, 999 mmol) and the reaction mixture was heated at 110° C. under argon for 25 hours. The reaction mixture was diluted with isopropyl acetate, cooled to room temperature, and 3 M hydrochloric acid (400 mL) was added slowly. The mixture was stirred at room temperature for 20 minutes, and the layers were separated. The organic layer was washed with 1 M hydrochloric acid (200 mL) and brine, then dried over magnesium sulfate, filtered and concentrated under a vacuum to provide the desired product as a brown oil (159 g). cooled to room temperature the layers were separated The organic layer was washed with 1 M hydrochloric acid (200 mL) and brine dried over magnesium sulfate filtered concentrated under a vacuum