Diisopropylamine → (2R,4S)-N-allyloxycarbonyl-2-(1-tert-butyldimethylsilyl-2,4-dioxoimidazolidin-5-ylmethyl)-4-tritylthiopyrrolidine

Participants

Reaction Steps

A 1.6M n-butyllithium-hexane solution (4.1 ml, 6.56 mmol) was dropwise added to a solution of diisopropylamine (1 ml, 7.14 mmol) in tetrahydrofuran (5 ml) under a nitrogen stream at -78° C., and the reaction solution was stirred at the same temperature for 10 minutes and under cooling with ice for 30 minutes. A solution of N,N'-bis(tert-butyldimethylsilyl)hydantoin (1.65 g, 5.02 mmol) in tetrahydrofuran (2 ml) was dropwise added to this reaction solution at -78° C. This solution was stirred at the same temperature for 1 hour. Then, hexamethylphosphoric triamide (1.75 ml, 10 mmol) was added to this reaction solution, and the mixture was stirred for 10 minutes. Then, a solution of (2S,4S)-N-allyloxycarbonyl-2-iodomethyl-4-tritylthiopyrrolidine (2.28 g, 4.00 mmol, compound of Reference Example 21-2) in tetrahydrofuran (3 ml) was dropwise added thereto. The reaction solution was stirred at the same temperature for 2 hours. To the reaction solution, a saturated ammonium chloride aqueous solution (10 ml) and ethyl acetate (300 ml) were added. The organic layer was washed sequentially with a 1N potassium hydrogen sulfate aqueous solution, water and a saturated sodium chloride aqueous solution and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to silica gel column chromatography (Wakogel™ C-300, hexane-ethyl acetate) to obtain (2R,4S)-N-allyloxycarbonyl-2-(1-tert-butyldimethylsilyl-2,4-dioxoimidazolidin-5-ylmethyl)-4-tritylthiopyrrolidine (1.19 g, yield: 45%).

Provenance & Evidence