1-tert-butyl 3-methyl (3R,6S)-6-methylpiperidine-1,3-dicarboxylate synthesis

Yield:1009377-05-2 71%

Reaction Conditions:

with triethylamine in dichloromethane at 0 - 20; for 19 h;

Steps:

Preparation of (3R,6S)-1-tert-Butyl 3-Methyl 6-Methylpiperidine-1,3-dicarboxylate (6-303β2-Me) To a solution of 6-313β2-Me (14 g) in CH₂Cl₂ (287 mL) and Et₃ N (50 mL, 4 equiv) was added 23.3 g (1.2 equiv) of Boc₂O at 0° C. After stirring at room temperature for 19 hours, GC-MS analysis indicated <1% of 6-313β1-Me remained. The reaction mixture was diluted with DI water (90 mL) and the phases were separated. The CH₂Cl₂ phase was washed with DI water (90 mL), dried (Na₂SO₄), filtered and concentrated to a residue. The residue was azeotroped with hexanes (2*250 mL) and purified by silica-gel chromatography (99:1 n-heptane/ethyl acetate) to afford 6-303β2-Me (16.3 g, 71%).

References:

US2010/93706,2010,A1 Location in patent:Page/Page column 51-52