反应详情

温度

65 °C

To an ethanol solution of (3 aS,4R,6S,6aR)-6-(2-hydroxyethoxy)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (approximately 100 kg in approximately 320 kg of to ethanol, prepared as described in WO01/92263) water (30 kg) was charged. The mixture was heated to 65° C. and oxalic acid×2H2O (57 kg) was added. Iso-propylacetate (665 kg) was added during 2 hours and the resulting slurry was cooled to 20° C. in 2 hours. The cooled slurry was kept at this temperature for additionally 2 hours. The precipitated product was isolated, washed with iso-propylacetate (141 kg) and dried under vacuum to give the title compound as a white solid (116 kg, approximately 82%). 1H NMR (400 MHz, DMSO-d6) δ 6.51 (app br s, NH2, COOH and OH protons), 4.70 (app d, J=6 Hz, 1H), 4.61 (app d, J=6 Hz, 1H), 3.91 (app br s, 1H), 3.40-3.59 (m, 5H), 2.12-2.23 (m, 1H), 1.89-2.01 (m, 1H), 1.36 (s, 3H), 1.23 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.7, 110.8, 82.8, 82.7, 82.1, 70.5, 60.0, 55.1, 32.5, 26.1, 23.9.

1. temperaturethe resulting slurry was cooled to 20° C. in 2 hours
2. customThe precipitated product was isolated
3. washwashed with iso-propylacetate (141 kg)
4. customdried under vacuum