Methyl iodide → 1-(1,1-Dimethylethyl) 2-methyl 5-oxo-1,2-piperidinedicarboxylate

1-(tert-Butoxycarbonyl)-5-oxopiperidine-2-carboxylic acid (2.0 g, 8.22 mmol) was dissolved in DMF (20 mL) under nitrogen and potassium carbonate (1.7 g, 12.33 mmol) was added, followed by iodomethane (620 μL, 9.95 mmol). The reaction mixture was stirred at room temperature under nitrogen for 23 h. Additional methyl iodide (256 μL, 4.11 mmol) was added and the reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (2×25 mL), then dried over sodium sulfate and concentrated to dryness. The crude residue was purified by flash column chromatography (Biotage), eluting with 0 to 100% ethyl acetate in heptanes, to afford the title compound (2.42 g, 53%) as a pale yellow oil. δH (250 MHz, CDCl3) 4.70 (dt, J 59.4, 6.3 Hz, 1H), 4.35 (dd, J 27.3, 19.0 Hz, 1H), 3.90 (dd, J 19.0, 12.4 Hz, 1H), 3.77 (s, 3H), 2.56-1.95 (m, 4H), 1.45 (s, 9H).

1. stirringthe reaction mixture was stirred at room temperature for 24 h
2. washwashed with saturated aqueous sodium bicarbonate solution (2×25 mL) and brine (2×25 mL)
3. dry with materialdried over sodium sulfate
4. concentrationconcentrated to dryness
5. customThe crude residue was purified by flash column chromatography (Biotage)
6. washeluting with 0 to 100% ethyl acetate in heptanes

ORD-Eintrag

ord-003f18351e3049e3961f0ee07f2504eb

Quelldatensatz

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09309243B2