Triethylamine → {(R)-3-[(R)-2-((S)-2-Amino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid

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Reaction Steps

{(R)-3-[(S)-2-((S)-2-Benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester and {(R)-3-[(R)-2-((S)-2-benzyloxycarbonylamino-3-phenyl-propionylamino)-3-methyl-butyrylamino]-2-hydroxy-propyl}-cyclohexylmethyl-phosphinic acid benzyl ester: To a solution of N—Z-Phe-Val-OH (1.0 g, 2.5 mmol) dissolved in CH2Cl2 (80 mL) under nitrogen was added hydroxybenzotriazole (0.346 g, 2.56 mmol) and PS-Carbodiimide (1.3 g, 3.0 mmol). After stirring for 10 min, triethylamine (1.4 mL, 10 mmol) and ((R)-3-amino-2-hydroxy-propyl)-cyclohexylmethyl-phosphinic acid benzyl ester hydrochloride (1.36 g, 3.75 mmol) were added. The reaction was stirred for 2 h, then filtered and concentrated in vacuo. The residue was purified by flash chromatography using 0-4% MeOH/CH2Cl2 as the eluent on a 35 g RediSep disposable column to give the title compound (0.806 g, 1.14 mmol) as a glassy solid. 31P NMR (CD3OD, 300 MHz): δ 59.09, 59.09, 58.38, 58.38. LCMS m/z: [M+H]+=707.

Provenance & Evidence