(R)-3-Amino-1-methyl-piperidine synthesis

Yield:1001353-92-9 72%

Reaction Conditions:

with formaldehyd;sodium cyanoborohydride in methanol;water at 20;

Steps:

163.I
163I. (R)-1-methylpiperidin-3-amine Sodium cyanoborohydride (4.51 g, 0.075 mol) was added in portion to a mixture of (R)-tert-butyl piperidin-3-ylcarbamate (10 g, 0.05 mol), 30% water solution of formaldehyde (7.5 mL), and methanol (75 mL) at 0° C. The reaction mixture was stirred at room temperature overnight and concentrated in vacuo. The residue was dissolved in ethyl acetate and water. After extraction, the organic layers were washed with water, brine, and dried over Na₂SO₄. Concentration in vacuo, gave the N-methyl compound as an oil which was used directly without further purification. To a solution of the crude material previously obtained in methanol (60 mL) was added 4N HCl dioxane (10 mL). The reaction mixture was stirred at room temperature for 6 h. After concentration in vacuo, the residue was triturated with ether. The resulting precipitate was filtered and washed with ice-cold methanol to give the title compound as a solid (4.01 g, 72%). ¹H NMR (CD₃OD, 400 MHz) δ 3.54 (1H, m), 2.81 (1H, m), 2.62 (1H, m), 2.23 (3H, s), 1.97 (1H, m), 1.67-1.87 (3H, m), 1.56-1.61 (1H, m), 1.41 (9H, s), 1.15-1.42 (1H, m).

References:

Bristol-Myers Squibb Company US2008/9497, 2008, A1 Location in patent:Page/Page column 72

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