Ammonia → Tert-butyl 2-cyanopiperidine-1-carboxylate

온도

-20 °C

Piperidine-1,2-dicarboxylic acid-1-tert-butyl ester (12.8 g, 55.6 mmol) and THF (170 mL) were added to a 500 mL round bottom flask equipped with stir bar. The solution was cooled to −20° C. and triethylamine (10.1 mL, 72.3 mmol) was added followed by ethyl chloroformate (5.32 mL, 55.6 mmol). The resulting white precipitate was left stirring at −10° C. for 1 h. Aqueous ammonia (22.6 mL, 1168 mmol) was added to the above reaction mixture and the clear reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and the isolated residue was dissolved in ethyl acetate (300 mL). The organic phase was successively washed with water (300 mL) and brine (200 mL), dried (sodium sulfate), filtered and concentrated in vacuo to isolate a clear gum. The gum was triturated with hexanes to isolate the title compound (9.4 g, 74%) as a white solid. 1H-NMR (CDCl3), δ(ppm): 6.03 (bs, 1H), 5.55 (bs, 1H), 4.77 (bs, 1H), 4.05 (bs, 1H), 2.81 (t, 1H), 2.27 (bs, 1H), 1.47 (m, 14H).

1. customequipped
2. waitThe resulting white precipitate was left
3. stirringstirring at −10° C. for 1 h
4. stirringthe clear reaction mixture was stirred at room temperature overnight
5. concentrationThe reaction mixture was concentrated in vacuo
6. dissolutionthe isolated residue was dissolved in ethyl acetate (300 mL)
7. washThe organic phase was successively washed with water (300 mL) and brine (200 mL)
8. dry with materialdried (sodium sulfate)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto isolate a clear gum
12. customThe gum was triturated with hexanes

ORD 기록

ord-31068ea7e3ba4a8ab43d092f97804004

출처 데이터셋

uspto-grants-2006_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07074809B2