反应详情

A mixture of 5.52 g (15.1 mmol) of benzyl (1R,4S)-4-(2,5-dimethyl-1H-pyrrol-1-yl)-1-(1-hydroxycyclobutyl)cyclopent-2-ene-1-carboxylate (Preparation SRT-0229), 8.20 g (120 mmol) of hydroxylamine hydrochloride, and 7.0 mL of 50% aqueous hydroxylamine (100 mmol) in 50 mL of methanol was heated at 68 C for 8 h, then cooled. Sufficient water was added to dissolve the crystals which deposited, and the solution was concentrated under reduced pressure to remove methanol. The resulting mixture was brought to pH ˜10 with aq. NaOH and then extracted with several portions of dichloromethane. The organic phase was dried over Na2SO4 and than concentrated under reduced pressure to afford 4.15 g (96%) of the title amine as a nearly colorless oil, of sufficient purity for the subsequent reaction. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.42-1.53 (m, 1H) 1.85 (dd, 1H) 1.88-2.08 (m, 4H) 2.19-2.27 (m, 1H) 2.46 (dd, J=14.5, 8.3 Hz, 1H) 3.97-4.02 (m, 1H) 4.70 (s, 1H) 5.16 (s, 2H) 5.84 (dd, J=5.6, 1.6 Hz, 1H) 5.98 (dd, J=5.6, 2.1 Hz, 1H) 7.31-7.38 (m, 5H). LC-MS ES+ 288.2

1. temperaturewas heated at 68 C for 8 h
2. temperaturecooled
3. dissolutionto dissolve the crystals which
4. concentrationthe solution was concentrated under reduced pressure
5. customto remove methanol
6. extractionextracted with several portions of dichloromethane
7. dry with materialThe organic phase was dried over Na2SO4
8. concentrationthan concentrated under reduced pressure