反应详情

温度

100 °C

Combine 4-(3-bromo-phenoxy)-cis 2-methyl-piperidine-1-carboxylic acid tert-butyl ester isomer 1 (preparation 22, 2.47 g, 6.67 mmol), benzhydrylideneamine (1.45 g, 8.0 mmol), toluene (100 mL), sodium-t-butoxide (0.9 g, 9.34 mmol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.17 g, 0.27 mmol), stir and heat at 100° C. After 10 min., add tris(dibenzylideneacetone)-dipalladium(0) (0.12 g, 0.13 mmol), stir and heat at 100° C. After 4 hr., cool to ambient temperature and partition between water (200 mL) and 4:1 hexane:ethyl acetate (200 mL). Separate organic layer, wash with water (100 mL) and aqueous NaCl solution (100 mL). Dry organic layer over sodium sulfate, filter and concentrate to an oil. Dissolve residue in methanol (80 mL) and treat with sodium acetate (1.31 g, 16.01 mmol) followed by hydroxylamine monohydrogen chloride (0.83 g, 12.0 mmol) with stirring. After 1 hr., partition between 4:1 hexane:ethyl acetate (200 mL) and 0.5 M aqueous sodium hydroxide solution (200 mL). Separate organic layer, wash with aqueous NaCl solution (100 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 (1.17 g, 59%). 1H NMR (CDCl3): 7.05 (m, 1H), 6.3 (m, 2H), 6.25 (m, 1H), 4.6 (m, 1H), 4.35 (m, 1H), 3.85 (m, 1H), 3.7 (bs, 2H), 3.25 (m, 1H), 1.95 (m, 2H), 1.8 (m, 1H), 1.7 (m, 1H), 1.45 (s, 9H), 1.3 (d, 3H).

1. stirringstir
2. temperatureheat at 100° C
3. waitAfter 4 hr
4. temperature, cool to ambient temperature
5. custompartition between water (200 mL) and 4:1 hexane
6. washSeparate organic layer, wash with water (100 mL) and aqueous NaCl solution (100 mL)
7. filtrationDry organic layer over sodium sulfate, filter
8. concentrationconcentrate to an oil
9. stirringwith stirring
10. waitAfter 1 hr
11. custom, partition between 4:1 hexane
12. washSeparate organic layer, wash with aqueous NaCl solution (100 mL)
13. dry with materialdry over sodium sulfate
14. filtrationfilter
15. concentrationconcentrate
16. washPurify residue by silica gel flash chromatography eluting with 4:1 hexanes