Ethyl Acetate → (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid

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Reaction Steps

(2R)-3-Cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl fluoride (4 g, 13.01 mmol) was added into the solution of (3S)-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidine carboxylic acid (3.91 g, 15.62 mmol) in dichloromethane (DCM) (46.1 ml), followed by adding Hunig's base (6.80 ml, 39.0 mmol). The reaction mixture was stirred at ambient temperature for 5 hrs. The reaction was diluted with DCM, and acetic acid (10 ml) was added. The resulting solution was washed with aqueous NH4Cl (200 ml). The aqueous solution was extracted with DCM (2×50 ml). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated to give a residue. Ethyl acetate (a few ml) was added. The desired product was filtered and washed with ethyl acetate. 3.21 g of desired product was collected as a white solid. The filtrate was purified by silica gel chromatography (0-100% ethyl acetate in hexane) to give a solid. The solid was added to 10 ml of MeCN. Another batch of the desired product (1.081 g) as a white solid was collected via filtration. These two batches of desired products were combined to yield (3S)-2-[(2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoyl]-1-{[(phenylmethyl)oxy]carbonyl}-3-pyrazolidinecarboxylic acid (4.291 g, 7.98 mmol, 61% yield). MS (ES+) m/z 538.0 (MH+).

Provenance & Evidence