反应详情

A mixture of trans-4-(4-hydroxyphenyl)cyclohexylamine 5 (0.35 g, 1.8 mmol) and mesylate 7 (0.32 g, 1.5 mmol) in THF (15 mL) was refluxed under N2 for 17 hours. The reaction mixture was diluted with EtOAc (40 mL) and washed with H2O, then saturated NaCl, dried (Na2SO4), filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 99:1 CHCl3:MeOH to 97:3 CHCl3:MeOH) and conversion to the maleate salt gave trans-4-[4-(3-phenylprop-2-ynylamino)cyclohexyl]phenol (160 mg, 26%) as a white solid: mp 171-179° C.; IR (KBr): 2938, 1700, 1516cm−1; 1H NMR (300 MHz, CD3OD) δ 7.52-7.35 (m, 5H), 7.04 (d, J=8 Hz, 2H), 6.69 (d, J=8 Hz, 2H), 6.25 (s, 2H), 4.21 (s, 2H), 3.45-3.35 (obs m, 1H) 2.52-2.42 (m, 1H), 2.31-2.20 (m, 2H), 2.05-1.60 (m, 2H), 1.67-1.48 (m, 4H); CI-MS (methane) (m/z): 306 [M+H]+; HPLC: method A, 7.63 minutes (97.9%); method B, 14.01 minutes (97.6%); Anal. Calcd for C21H23NO.C4H4O4: C, 71.24; H, 6.46; N, 3.32. Found: C, 71.21; H, 6.51; N, 3.22.

1. temperaturewas refluxed under N2 for 17 hours
2. washwashed with H2O
3. dry with materialsaturated NaCl, dried (Na2SO4)
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customPurification by flash chromatography (silica, 99:1 CHCl3:MeOH to 97:3 CHCl3:MeOH) and conversion to the maleate salt