Chlorotrimethylsilane → 3-(1-Methylallyl)piperidine-1,3-dicarboxylic acid 1-tert-butyl ester

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Reaction Conditions

Reaction Steps

To a solution of piperidine-1,3-dicarboxylic acid 3-((Z)-but-2-enyl)ester 1-tert-butyl ester (68.3 g) in tetrahydrofuran (700 ml) cooled to −74° C. was added lithium hexamethyl disilazide (1.6M tetrahydrofuran solution, 166 ml). The reaction mixture was warmed to 0° C. over 35 minutes, stirred at the same temperature for additional 25 minutes, and cooled to −74° C. again. To the mixture was added trimethylsilyl chloride (39.6 ml). The reaction mixture was warmed to room temperature over 70 minutes, and stirred at the same temperature for additional 4 hours. To the mixture were sequentially added water (600 ml), 2M aqueous sodium hydroxide solution (70 ml), and the mixture was washed with n-hexane (600 ml). The separated aqueous layer was acidified by 2M aqueous hydrochloric acid solution, followed by extracted with ethyl acetate (300 ml, 200 ml, 150 ml) three times. The combined organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was slurry-washed with n-hexane/ethyl acetate solution (10/1) to give the titled compound (42.5 g).

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