1,2-Dichloroethane → 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-L-prolinamide

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(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid (WO 2003101442, 38.2 g, 0.125 mol), L-prolinamide (14.3 g, 0.125 mol,) N-methyl morpholine (34.4 mL, 0.313 mol,) and HOBt (18.65 g, 0.138 mol) were dissolved in DMF (400 mL) with stirring. EDC (26.46 g, 0.138 mol) was added portionwise and the solution was stirred at room temperature for 3 hours. The majority of the DMF was removed in vacuo and the residue was diluted with ethyl acetate (1 L.) This solution was washed with cold 0.5M HCl solution (200 mL), twice with water (200 mL), saturated aqueous NaHCO3 solution, brine, and then dried over MgSO4. After filtering and evaporating, the crude material was dissolved in hot ethyl acetate (˜150 mL) with stirring. While keeping the solution hot, hexanes (˜150 mL) was added until the solution was cloudy. Cooling slowly to room temperature while stirring gave a thick slurry. The solid was filtered off and washed with 1:1 ethyl acetate:hexanes, followed by a wash with hexanes. After drying, the product 1-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-L-prolinamide was obtained as a white solid (34.4 g, 69% yield). LC/MS m/z 402 (MH+)

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