Acetic Acid → (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N'-isobutyl-hydrazide

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Reaction Steps

(step 1) To a solution of 4.4 g (9.6 mmol) (2S,4R)-4-(4-Methoxy-benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid in 200 ml CH2Cl2 were added 1.2 g (10.8 mmol,1.1 eq) N-hydroxy-2-pyridone, followed by 2.2 g (10.7 mmol, 1.1 eq) N, N-dicyclohexylcarbodiimide in 25 ml CH2Cl2 at 0° C. over a period of 30 min. The suspension was stirred for additional 4 h at that temperature before 4.2 ml (33.0 mmol, 3.4 eq) NEM and 1.9 g (mmol, 1.05 eq) isobutylhydrazine.sulfate were added. The reaction mixture was stirred at RT over night. The suspension was treated with 0.55 ml (9.6 mmol, 1.0 eq) glacial acetic acid in 10 ml water and stirred for 1.5 h, diluted with aq. NaHCO3 (5%) and extracted with CH2Cl2. The combined organic phases were washed with 1M KHSO4 solution, water and brine, dried over Na2SO4 and evaporated. Tituration with hexane yields 5.02 g (quant) (2S,4R)-4-(4-Methoxy -benzylsulfanyl)-1-(naphthalene-2-sulfonyl)-pyrrolidine-2-carboxylic acid N′-isobutyl-hydrazide, which was directly subjected to the following reaction.

Provenance & Evidence