Methyl iodide → 1-Piperidinecarboxylic acid, 4-methoxy-3,3-dimethyl-, 1,1-dimethylethyl ester, (4S)-

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To a solution of (S)-tert-butyl 4-hydroxy-3,3-dimethylpiperidine-1-carboxylate (6.43 g, 28.0 mmol) in DMF (100 mL) at 0° C. was added NaH (60% dispersion in mineral oil, 2.24 g, 56.1 mmol), and the reaction mixture was stirred at room temperature for 15 min. Then, MeI (3.16 mL, 50.5 mmol) was added dropwise and the resulting mixture was stirred at room temperature for 1.5 h. The reaction mixture was then cooled to 0° C. and sat. aq. NH4Cl was added slowly and stirred for 5 min. The solution was warmed to room temperature and diluted with water (250 mL) and extracted with Et2O (3×200 mL). The combined organic extracts were washed with brine (100 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (5-30% EtOAc/heptane) to provide (S)-tert-butyl 4-methoxy-3,3-dimethylpiperidine-1-carboxylate. 1H NMR (400 MHz, CDCl3) δ ppm 3.75 (br. s., 1 H), 3.41 (d, J=13.1 Hz, 1 H), 3.35 (s, 3 H), 3.09 (ddd, J=13.3, 9.3, 3.7 Hz, 1 H), 2.86 (dd, J=8.5, 3.7 Hz, 1 H), 2.80 (d, J=13.1 Hz, 1 H), 1.74-1.85 (m, 1 H), 1.48-1.59 (m, 1 H), 1.46 (s, 9 H), 0.94 (s, 3 H), 0.88 (s, 3 H).

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