Triethylamine → (S)-1'-[2-t-Butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]spiro[2H-1-benzopyran-2,4'-piperidin]-4-(3H)-one

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Reaction Steps

Triethylamine (0.50 mL, 0.36 g, 3.6 mmol) was added to a stirred, cooled (0° C.) mixture of (S)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionic acid (364 mg, 1 mmol), spiro[2H-1-benzopyran-2,4'-piperidin]-4-(3H)-one hydrochloride (U.S. Pat. No. 5,206,240, Example 67A) (254 mg, 1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol) and 1-hydroxybenzotriazole (162 mg, 1.2 mmol) in dimethylformamide (5 mL) and the mixture was stirred at room temperature for 2 h. Aqueous sodium hydrogen carbonate (saturated, 20 mL) and water (10 mL) were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic fractions were washed with aqueous citric acid (10%, 2×20 mL), aqueous sodium hydrogen carbonate (saturated, 2×20 mL) and brine (20 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH (99.5:0.5 increasing to 98:2) to give the title compound as a colorless foam (248 mg, 44%). m/e (ES+) 563 (MH+).

Provenance & Evidence