158406-99-6

General procedure for the synthesis of tert-butyl (S)-3-(bromomethyl)piperidine-1-carboxylate from tert-butyl (S)-3-(hydroxymethyl)piperidine-1-carboxylate: tert-butyl (S)-3-(hydroxymethyl)piperidine-1-carboxylate (30.0 g, 139 mmol) and carbon tetrabromide (72.0 g, 217 mmol) were dissolved in dichloromethane (150 mL). A solution of triphenylphosphine (42.4 g, 162 mmol) in dichloromethane (150 mL) was slowly added dropwise under ice bath cooling, keeping the internal temperature of the reaction system between 20 and 25 °C. After the dropwise addition was completed, the reaction mixture was continued to be stirred at room temperature for 1 hour. Subsequently, cyclohexane (500 mL) was added and about half of the solvent was removed by evaporation under reduced pressure. The remaining solution was cooled in an ice bath and filtered to remove the resulting precipitate. The filtrate was concentrated under reduced pressure and the resulting residue was purified by fast column chromatography (eluent: 0 to 25% ethyl acetate/hexane, silica gel as stationary phase) to afford 35.1 g (91% yield) of tert-butyl (S)-3-(bromomethyl)piperidine-1-carboxylate as a solid. Mass spectrum (electrospray positive ion mode) m/z 278 ([M+H]+).

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[2] Journal of Medicinal Chemistry, 2008, vol. 51, # 18, p. 5663 - 5679
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[4] Patent: US2008/176901, 2008, A1. Location in patent: Page/Page column 9-10