反应详情

To a suspension of trans-3-(4-hydroxyphenyl)-N-(4-phenylcyclohexyl)propionamide (0.65 g, 2.0 mmol) in toluene (5 mL), under a nitrogen atmosphere, was added DIBAL-H (12.0 mL of a 1 M in toluene, 12 mmol) with stirring. The reaction mixture was heated under reflux overnight. Additional DIBAL-H (12 mL of a 1.0 M solution in toluene, 12 mmol) was added, and heating was continued for a further 1.5 hours. The reaction mixture was cooled to room temperature and quenched by the slow addition of MeOH (50 mL). The mixture was heated at reflux for 15 minutes, cooled to room temperature, filtered, and concentrated under reduced pressure. Purification by flash chromatography (silica, 10% MeOH:CH2Cl2) then (silica, 89:10:1 CH2Cl2: MeOH:NH4OH) gave (b) trans 4-[3-(4-phenylcyclohexylamino)propyl]phenol (110 mg) as a tan solid: mp 211-214° C.; IR (KBr): 2926, 1516, cm−1; 1H NMR (300 MHz, CD3OD) δ 7.23-7.10 (m, 5H), 7.02 (d, J=8 Hz, 2H), 6.69 (d, J=8 Hz, 2H), 2.68-2.44 (m, 6H), 2.04 (br d, J=13 Hz, 2H), 1.88 (br d, J=13 Hz, 2H), 1.82-1.73 (m, 2H), 1.57 (dddd, J=13, 13, 13, 3 Hz, 2H), 1.26 (dddd, J=13, 13, 13, 3 Hz, 2H); CI—MS (methane) (m/z): 310 [M+H]+; HRMS-API (m/z): [M+H]+ calculated for C21H27NO, 310.2171; found, 310.2166; HPLC: method A, 7.93 minutes (95.2%); method B, 14.29 minutes (97.3%); Anal. Calcd. for C21H27NO.0.80H2O: C, 77.88; H, 8.90; N, 4.32. Found: C, 77.52; H, 8.66; N, 4.12.

1. temperatureThe reaction mixture was heated
2. temperatureunder reflux overnight
3. temperatureheating
4. customquenched by the slow addition of MeOH (50 mL)
5. temperatureThe mixture was heated
6. temperatureat reflux for 15 minutes
7. temperaturecooled to room temperature
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by flash chromatography (silica, 10% MeOH:CH2Cl2)