(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮 → 3-(2-Acetylamino-2-methoxycarbonylvinyl)pyridinium Tetrafluoroborate

HRID 7203

反应方程式

HRID 7203 反应方程式
C[C:2]1[O:3][C:4](=[O:14])/[C:5](=[CH:7]/[C:8]2[CH:9]=[N:10][CH:11]=[CH:12][CH:13]=2)/[N:6]=1.[CH2:15](N(CC)CC)C.[F:22][B-:23]([F:26])([F:25])[F:24].[H+].C(OC)(C)(C)C.[CH3:34][OH:35]>>[F:22][B-:23]([F:26])([F:25])[F:24].[C:34]([NH:6][C:5]([C:4]([O:3][CH3:2])=[O:14])=[CH:7][C:8]1[CH:9]=[NH+:10][CH:11]=[CH:12][CH:13]=1)(=[O:35])[CH3:15]

参与物

6

反应物 5

HCID 887(5BETA,17BETA)-17-羟基-17-(甲基-D3)-2'H-雄甾-2-烯并[3,2-C]吡唑-5'(1'H)-酮HCID 8471三乙胺HCID 15413甲基叔丁基醚HCID 28118氟硼酸HCID 17316032-methyl-4-(3-pyridinylmethylene)-5(4H)-oxazolone

产物 1

HCID 865837833-(2-Acetylamino-2-methoxycarbonylvinyl)pyridinium Tetrafluoroborate

反应条件

温度
60 °C

实验过程

Under nitrogen, a suspension of 2-methyl-4-[pyridin-3-yl-(Z)-methylene]-4H-oxazol-5-one (12.0 kg, 63.83 mol) in methanol (120.0 l) was heated at 60° C. Triethylamine (0.5 l) was pumped in, and the apparatus was rinsed with methanol (0.5 l) (the pH of a sample taken, measured using a glass electrode, was pH 8.15). Within a period of 30 min, the reaction solution was cooled to 30° C. Tetrafluoroboric acid solution (48% strength in water, 11.8 kg, 64.5 mol) was added over a period of 30 min. Within 1 h, the mixture was cooled to an internal temperature of 10° C. and (if required after seeding) the suspension was then stirred at 10° C. for a further 3 h. Methyl tert-butyl ether (40.0 l) was added, and the mixture was stirred at 10° C. for 1 h. The suspension was introduced into a centrifuge which had been inertized with nitrogen, centrifuged, and the the product washed with methyl tert-butyl ether (20.0 l) and dried at 40° C. under reduced pressure. Yield: 18.7 kg (60.71 mol, 95.1% of theory). M.p.: 179.4° C.; MS (ESI+): m/z (%)=221 ([M+H+] of the free base, 100); 1H-NMR (200 MHz, DMSO-d6): δ=2.01 (s, 3H), 3.77 (s, 3H), 7.21 (s, 1H), 7.89 (dd, 1H), 8.48 (d, 1H), 8.76 (d, 1H), 8.98 (s, 1H), 9.92 (s, 1H); IR (KBr): ν=1726.9, 1670.1, 1091.5 cm−1.

后处理

  1. washwas rinsed with methanol (0.5 l) (the pH of a sample
  2. temperaturethe reaction solution was cooled to 30° C
  3. waitWithin 1 h
  4. temperaturethe mixture was cooled to an internal temperature of 10° C. and (if required after seeding) the suspension
  5. stirringthe mixture was stirred at 10° C. for 1 h
  6. additionThe suspension was introduced into a centrifuge which
  7. washcentrifuged, and the the product washed with methyl tert-butyl ether (20.0 l)
  8. customdried at 40° C. under reduced pressure

来源与证据

ORD记录
ord-48f84ae397d440298551c751c46bf209
来源数据集
uspto-grants-2006_08
专利号
US07084250B2

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