919286-71-8

The general procedure for the synthesis of tert-butyl (S)-2-(bromomethyl)morpholine-4-carboxylate from (S)-N-Boc-2-hydroxymethylmorpholine was as follows: (S)-N-Boc-2-hydroxymethylmorpholine (6.9 g, 0.032 mol) and carbon tetrabromide (15.8 g, 0.048 mol) were dissolved in dichloromethane (100 mL) and cooled in an ice bath to 0°C. A solution of triphenylphosphine (12.2 g, 0.046 mol) in dichloromethane (100 mL) was added slowly and dropwise over 30 minutes. The reaction temperature was maintained at 0 °C with stirring for 1 h. The reaction was gradually warmed to room temperature and stirring was continued overnight. Upon completion of the reaction, the reaction solution was concentrated to 1/2 of the original volume by distillation under reduced pressure, followed by filtration of the concentrate through a pad of silica gel and elution of the target product with a hexane solution of 15% ethyl acetate as eluent. The filtrate containing the product was collected and the solvent was removed by concentration under reduced pressure to afford tert-butyl (S)-2-(bromomethyl)morpholine-4-carboxylate as a colorless oil (8 g, 90% yield). Mass spectrometry (electrospray ionization, positive ion mode) showed m/e 281 [M + H]+.

[1] Patent: WO2008/121685, 2008, A1. Location in patent: Page/Page column 44
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