tert-butyl 3-(isopropylamino)piperidine-1-carboxylate synthesis

Yield:1282742-29-3 82%

Reaction Conditions:

Stage #1: 3-oxo-piperidine-1-carboxylic acid tert-butyl ester;isopropylaminewith methanol at 20; for 1 h;
Stage #2: with sodium tetrahydroborate at 0 - 20;
Stage #3: with waterCooling with ice;

Steps:

52

Synthesis is ieri-butyl 3-(isopropylamino)piperidine-l-carboxylate: A solution teri-butyl 3-oxopiperidine-l-carboxylate (2 g, 10.03 mmol) and 2-aminopropane (710 mg, 12. mmol) in MeOH (40 mL) was stirred at rt for 1 h. To the solution was added NaBH₄ (758 n 20.06 mmol) at 0 °C and the reaction mixture was stirred at rt for 12h. The reaction mixture w diluted with ice-cooled water and the solvent was reduced to afford a residue which was w dissolved in CH₂C1₂ and washed with water. The organic layer was dried over Na₂S0₄, concentrated in vacuo and purified by column chromatography (silica gel, gradient MeOH in CH₂C1₂) to afford the titled compound (2 g, 82%). 1H NMR (400 MHz, CDC1₃): δ 4.01-3.90 (m, IH), 3.78 (dt, J = 3.6, 9.2 Hz, IH), 3.48 (s, IH), 2.96 (heptate, J = 6.4 Hz, IH), 2.92-2.79 (m, IH), 2.69-2.55 (m, IH), 1.90-1.87 (m, IH), 1.68-1.61 (m, IH), 1.46 (s, 9H), 1.29-1.18 (m, 2H), 1.05 (d, J = 6.0 Hz, 6H). ES-MS: m/z [M+l] = 243.

References:

WO2012/58645,2012,A1 Location in patent:Page/Page column 115-116