Citric Acid → 4-[(R)-2-iodo-1-(methyl)ethyl]pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester

Participants

Reaction Steps

Triethylamine (2.7 mL, 19.1 mmol) and mesyl chloride (1.2 mL, 15.3 mmol) were added to a solution of 4-[(R)-2-hydroxy-1-(methyl)ethyl]pyrrolidine-1,3-dicarboxylic acid 1-benzyl ester 3-methyl ester (4.1 g, 12.8 mmol) in dichloromethane (100 mL) under ice-cooling, and then the mixture was stirred at room temperature for 30 minutes. After adding methanol to the reaction mixture, the mixture was blended with a mixture of ethyl acetate and a 10% citric acid solution. The organic layer was washed with brine and dried over magnesium sulfate. After filtration, the solvent was evaporated under reduced pressure, and the resulting residue was dissolved in acetone (100 mL). Sodium iodide (4.1 g, 27.4 mmol) was added, and the mixture was heated to reflux for 20 hours. The reaction mixture was cooled and then the solvent was evaporated under reduced pressure. The resulting residue was blended with a mixture of ethyl acetate and water. The organic layer was washed with a saturated sodium thiosulfate solution and brine, dried over magnesium sulfate, and then filtered, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0→7:3) to give 5.0 g (84%) of the diastereomer mixture title compound as a colorless oil. The diastereomers were used for the next step without separation.

Provenance & Evidence