Phosgene → (3s)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1r)-1-phenylethyl]amino}ethyl)pentylcarbamate

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Reaction Steps

Phosgene (1.04 mL, 1.93 M, 2.00 mmol) was added dropwise to a solution of (S)-(+)-pantolactone (130 mg, 1.00 mmol) and quinoline (0.241 mL, 2.00 mmol) in anhydrous tetrahydrofuran (3 mL) at 0° C. under nitrogen. The cold bath was removed, and the mixture was stirred for 18 h at room temperature. Volatiles were then removed under vacuum, and the resulting solid was slurried in anhydrous tetrahydrofuran (4 mL) under nitrogen. A solution of triethylamine (0.153 mL, 1.10 mmol) and (3S)-3-amino-2-hydroxy-N-[(1R)-1-phenylethyl]heptanamide (264 mg, 1.00 mmol) in anhydrous tetrahydrofuran was added. The resulting mixture was stirred for 18 h, and was then partitioned between ethyl acetate (70 mL) and 1 N hydrochloric acid (35 mL). The ethyl acetate layer was washed further with two 35 mL portions of 1 N hydrochloric acid, followed by saturated aqueous sodium chloride (35 mL). After drying over magnesium sulfate, volatiles were removed to afford (3S)-4,4-dimethyl-2-oxotetrahydro-3-furanyl (1S)-1-(1-hydroxy-2-oxo-2-{[(1R)-1-phenylethyl]amino}ethyl)pentylcarbamate as a tan oil (358 mg, 85%).

Provenance & Evidence