L-Hydroxyproline → (2S,3R)-1-(3-Chloro-4-cyano-2-methylphenylcarbamoyl)-3-hydroxypyrrolidine-2-carboxylic acid methyl ester

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Reaction Steps

To a solution of hydroxyproline compound 1F (493 mg, 3.40 mmol) in CH2Cl2 (15 mL) was added 4 Å molecular sieves (˜3.0 g), followed by isocyanate 23E (725 mg, 3.22 mmol), and the resulting mixture was stirred at rt overnight, filtered, and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, 0.5% MeOH in EtOAc/hexane, 1:1) to afford the title compound (736 mg) as an off-white solid. HPLC column: YMC S-5 C18 (4.6×50 mm), 0% to 100% B, 4 min gradient, 1 min hold (A=90% H2O—10% CH3CN—0.1% TFA and B=10% H2O—90% CH3CN—0.1% TFA), flow rate at 4 mL/min, UV detection at 220 nm, 1.57 min retention time (100%); MS (ES) m/z 338 [M+H]+.

Provenance & Evidence