3-Piperidineacetic acid, 1-[(1,1-dimethylethoxy)carbonyl]-4-oxo-, 1,1-dimethylethyl ester

Synthesis

5292-43-3

1010814-94-4

To a tetrahydrofuran (THF, 300 mL) solution of diisopropylamine (13.5 mL, 96 mmol) was slowly added n-butyllithium (n-BuLi, 2.5 M in hexane, 32 mL) dropwise at -78 °C. The reaction mixture was slowly warmed to -10 °C and then cooled to -78 °C again. Subsequently, a solution of tert-butyl 4-oxopiperidine-1-carboxylate (10 g, 50 mmol) in THF (50 mL) was added dropwise and stirring was continued for 15 min at -78 °C. Next, a mixed solution of tert-butyl bromoacetate (12.6 mL, 85 mmol) with HMPT (5 mL) in THF (30 mL) was added dropwise, and the reaction mixture was stirred at -78 °C for 4 h before slowly warming up to room temperature. The reaction mixture was quenched with saturated aqueous ammonium chloride (NH4Cl) and extracted with ethyl acetate (EA). After post-treatment and purification by column chromatography (eluent: n-hexane/ethyl acetate=4:1), the target product tert-butyl 3-(2-tert-butoxy-2-oxoethyl)-4-oxopiperidine-1-carboxylate was obtained as 7.6 g (50.6% yield, yellow oil).1H NMR (CDCl3) δ: 4.40-4.20 (m, 2H); 3.25-3.15 (m, 1H). 1H); 3.00-2.80 (m, 2H); 2.70-2.40 (m, 3H); 2.30-2.10 (m, 1H); 1.51 (s, 9H), 1.46 (s, 9H).

References