反应详情

温度

70 °C

Dissolve 4-hydroxy-cis-2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 2, 2.53 g, 11.75 mmol) in 1-methyl-2-pyrrolidinone (50 mL) and treat with 95% sodium hydride (0.33 g, 12.93 mmol), stir and heat at 70° C. After 1 hr., add 1-bromo-3-fluoro-benzene (1.44 mL, 12.93 mmol), stir and heat at 100° C. After 16 hr., cool to ambient temperature and quench with water (100 mL). Extract with 4:1 hexane:ethyl acetate (2×100 mL). Combine the organic layers and wash with aqueous NaCl solution (75 mL), dry over sodium sulfate, filter and concentrate. Purify residue by silica gel flash chromatography eluting with 4:1 hexanes:ethyl acetate to obtain the title compound (2.47 g, 57%). 1H NMR (CDCl3): 7.15 (m, 1H), 7.05 (m, 2H), 6.8 (dd, 1H), 4.6 (m, 1H), 4.35 (m, 1H), 3.9 (m, 1H), 3.25 (m, 1H), 1.9 (m, 3H), 1.75 (m, 1H), 1.5 (s, 9H), 1.3 (d, 3H).

1. dissolutionDissolve
2. stirringstir
3. temperatureheat at 100° C
4. waitAfter 16 hr
5. temperature, cool to ambient temperature
6. customquench with water (100 mL)
7. extractionExtract with 4:1 hexane
8. washCombine the organic layers and wash with aqueous NaCl solution (75 mL)
9. dry with materialdry over sodium sulfate
10. filtrationfilter
11. concentrationconcentrate
12. washPurify residue by silica gel flash chromatography eluting with 4:1 hexanes