Diethanolamine → tert-butyl (4S)-4-hydroxy-3,3-dimethyl-piperidine-1-carboxylate

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To a solution of tert-butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (10.0 g, 44.0 mmol) in THF (45 mL) at 0° C. was added dropwise (−)-DIP-Chloride (50-65 wt. % in heptane, 48.9 mL, 79.0 mmol), and the reaction mixture was stirred at 5° C. for 4 days. The reaction mixture was then diluted with Et2O (250 mL) and diethanol amine (8.0 g) was added to give a massive amount of white precipitate. The resulting mixture was vigorously stirred at room temperature for 3 h. The heterogeneous mixture was then filtered through a Buchner funnel packed with Celite®, and the resulting filtrate was concentrated to give a yellow residue. The residue was purified by silica gel chromatography (25-70% EtOAc/heptane) to provide (S)-tert-butyl 4-hydroxy-3,3-dimethylpiperidine-1-carboxylate. (90% ee). Enantiomeric excess determined by Mosher ester analysis. 1H NMR (400 MHz, CDCl3) δ ppm 3.79-3.94 (m, 1 H), 3.53 (d, J=13.4 Hz, 1 H), 3.42 (dd, J=9.2, 4.2 Hz, 1 H), 3.05 (ddd, J=13.2, 9.8, 3.5 Hz, 1 H), 2.74 (d, J=13.1 Hz, 1 H), 1.69-1.80 (m, 2 H), 1.58 (m, 1 H), 1.46 (s, 9 H), 0.97 (s, 3 H), 0.90 (s, 3 H).

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