反应详情

A solution of 212 (2.1 g, 6.5 mmol) in EtOH (60 ml) with 10% NaOH (15 ml) was heated under reflux for 20 h. A further 15 ml of 10% NaOH was added and heating continued for another 24 h. The reaction mixture was cooled to rt and concentrated to remove the EtOH. Chloroform (30 ml) was added, the layers separated and the aqueous layers extracted with chloroform (3×). The combined organic layers were dried (MgSO4) and concentrated in vacuo to afford an orange oil. Purification by flash column chromatography eluting with EtOAc to 20% MeOH/80% EtOAc/0.5% TEA afforded the title compound (858 mg, 47%) as an orange powder. 1H NMR (270 MHz; CDCl3) 1.20 (3H, d, J=6.4 Hz, CH3CH), 1.46 (1H, brs, NH), 2.35 (1H, dd, J=15.8, 10.6 Hz, CHH), 2.61 (1H, dd, J=15.8, 3.7 Hz, CHH), 2.88-3.0 (1H, m, CH3CH), 3.83 (3H, s, OCH3), 3.93 (1H, d, J=15.6 Hz, one of ArCH2N), 4.04 (1H, d, J=15.6 Hz, one of ArCH2N), 5.09 (2H, s, CH2Ph), 6.54 (1H, s, CH), 6.57 (1H, s, CH), 7.25-7.43 (5H, m, 5×CH, phenyl). 13C NMR (67.5 MHz; CDCl3) 22.60 (CH3), 36.76 (CH2), 48.43 (CH2), 49.37 (CH), 56.16 (OCH3), 71.23 (CH2), 109.51 (CH), 114.75 (CH), 126.82 (C), 127.37 (CH), 127.82 (CH), 128.09 (C), 128.59 (CH), 137.41 (C), 146.62 (C), 148.0 (C). LC/MS (ES+) tr=1.21 min, m/z 284.13 (M++H). HPLC tr=2.49 min (>99%).

1. temperatureunder reflux for 20 h
2. temperatureheating
3. concentrationconcentrated
4. customto remove the EtOH
5. additionChloroform (30 ml) was added
6. customthe layers separated
7. extractionthe aqueous layers extracted with chloroform (3×)
8. dry with materialThe combined organic layers were dried (MgSO4)
9. concentrationconcentrated in vacuo
10. customto afford an orange oil
11. customPurification by flash column chromatography
12. washeluting with EtOAc to 20% MeOH/80% EtOAc/0.5% TEA