Iodine → 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

Participants

Reaction Steps

To as solution of ethyl (3S,4R)-4-{[(4-chloro-3-cyano-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-(prop-2-en-1-yloxy)piperidine-1-carboxylate (Intermediate 21, 1.1 g, 2.79 mmol) in toluene (190 mL) was added iodine (2.9 g, 11.16 mmol) followed by hexamethyldisilane (4.65 mL, 22.33 mmol). The reaction mixture was heated to reflux for 30 h and then cooled to room temperature. The reaction mixture was treated 10% sodium thiosulphate (150 mL) and the layers were separated. The aqueous layer was extracted with toluene and the organic layer was dried over anhydrous sodium sulphate and concentrated under reduced pressure. Purification by column chromatography (silica, 4% methanol in dichloromethane) afforded 300 mg (33%) of 4-chloro-3-cyano-5-methyl-N-[(3S,4R)-3-(prop-2-en-1-yloxy)piperidin-4-yl]-1H-pyrrole-2-carboxamide

Provenance & Evidence