1,2-Dichloroethane → (2R,5R)-2,5-bis(4-fluorobenzyl)-6-oxo-6-((S)-2-oxo-1-phenylazepan-3-ylamino)hexanoic acid

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Reaction Steps

EDC (16 mg, 0.083 mmol) was added to a 0° C. solution of (2R,5R)-2,5-Bis(4-fluorobenzyl)hexanedioic acid (30 mg, 0.083 mmol) in DMF (1 mL) and DCM (5 mL). The ice bath was removed and the reaction mixture was stirred at rt overnight. The reaction mixture was concentrated to remove most of the DCM. (S)-3-Amino-1-phenylazepan-2-one (21 mg, 0.085 mmol) was added followed by TEA (18.4 mg, 0.182 mmol). The reaction mixture was left to stir at rt for 3 hr. The reaction mixture was partitioned between EtOAc and 5% aqueous KHSO4. The organic phase was isolated, washed with saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. The crude product was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-100% EtOAc/Hex to give (2R,5R)-2,5-bis(4-fluorobenzyl)-6-oxo-6-((S)-2-oxo-1-phenylazepan-3-ylamino)hexanoic acid (32 mg, 0.058 mmol, 71% yield) as a colorless syrup. Anal. Calcd. for C32H34F2N2O4 m/z 548.3. found: 549.1 (M+H)+.

Provenance & Evidence