4-Methylnicotinic acid Hydrochloride → 4-Methylpiperidine-3-carboxylic acid hydrochloride

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Reaction Steps

4-Methylnicotinic acid hydrochloride (5.00 g, 36.5 mmol, ASDI) and platinum (IV) oxide (0.35 g, 1.54 mmol) were shaken in AcOH (100 mL) at about 60 psi hydrogen for about 72 h. The reaction mixture was filtered through Celite® and concentrated under reduced pressure to give 4-methylpiperidine-3-carboxylic acid hydrochloride (7.4 g, contained residual AcOH) that was carried forward without additional purification. To a solution of the acid (7.40 g, 36.4 mmol) and NaHCO3 (15.3 g, 182 mmol) in MeCN (75 mL) and water (125 mL) was added Boc2O (11.0 mL, 47.3 mmol). The reaction was stirred at about 25° C. for about 16 h. The reaction mixture was diluted with Et2O (100 mL) and acidified to pH 1 with 4N aqueous HCl. The layers were separated and the organic solution was washed with brine (2×100 mL), dried over anhydrous Na2SO4, filtered, and concentrated. A white solid formed that was triturated with heptane and collected by vacuum filtration to give 1-(tert-butoxycarbonyl)-4-methylpiperidine-3-carboxylic acid (5.2 g, 58% over 2 steps): LC/MS (Table 2, Method a) Rt=2.01 min; MS m/z: 242 (M−H)−.

Provenance & Evidence