3-吡啶甲醛 → (E)-2-(吡啶-3-亚甲基)奎宁环素-3-酮

HRID 45284

反应方程式

HRID 45284 反应方程式
Cl.[N:2]12[CH2:9][CH2:8][CH:5]([CH2:6][CH2:7]1)[C:4](=[O:10])[CH2:3]2.[OH-].[K+].[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1>CO>[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=[C:3]2[C:4](=[O:10])[CH:5]3[CH2:8][CH2:9][N:2]2[CH2:7][CH2:6]3)[CH:14]=1

参与物

5

反应物 3

HCID 103713-吡啶甲醛HCID 14797氢氧化钾HCID 1020191-Azabicyclo(2.2.2)octan-3-one, hydrochloride (1:1)

产物 1

HCID 611822(E)-2-(吡啶-3-亚甲基)奎宁环素-3-酮收率 89.3%

试剂、催化剂与溶剂 1

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)-酮溶剂

实验过程

3-Quinuclidinone hydrochloride (8.25 kg, 51.0 mol) and methanol (49.5 L) were added to a 100 L glass reaction flask, under an nitrogen atmosphere, equipped with a mechanical stirrer, temperature probe, and condenser. Potassium hydroxide (5.55 kg, 99.0 mol) was added via a powder funnel over an approximately 30 min period, resulting in a rise in reaction temperature from 50° C. to 56° C. Over an approximately 2 h period, 3-pyridinecarboxaldehyde (4.80 kg, 44.9 mol) was added to the reaction mixture. The resulting mixture was stirred at 20° C.±5° C. for a minimum of 12 h, as the reaction was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction mixture was filtered through a sintered glass funnel and the filter cake was washed with methanol (74.2 L). The filtrate was concentrated, transferred to a reaction flask, and water (66.0 L) was added. The suspension was stirred for a minimum of 30 min, filtered, and the filter cake was washed with water (90.0 L) until the pH of the rinse was 7-9. The solid was dried under vacuum at 50° C.±5° C. for a minimum of 12 h to give 8.58 kg (89.3%) of 2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octan-3-one.

后处理

  1. customequipped with a mechanical stirrer
  2. customresulting in a rise in reaction temperature from 50° C. to 56° C
  3. customUpon completion of the reaction
  4. filtrationthe reaction mixture was filtered through a sintered glass funnel
  5. washthe filter cake was washed with methanol (74.2 L)
  6. concentrationThe filtrate was concentrated
  7. customtransferred to a reaction flask
  8. additionwater (66.0 L) was added
  9. stirringThe suspension was stirred for a minimum of 30 min
  10. filtrationfiltered
  11. washthe filter cake was washed with water (90.0 L) until the pH of the rinse
  12. customThe solid was dried under vacuum at 50° C.±5° C. for a minimum of 12 h

来源与证据

ORD记录
ord-cd5c7f120af947d0aff7634e24a6554d
来源数据集
uspto-grants-2013_09
专利号
US08541446B2

关联笔记

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