반응 #73562

반응 방정식

3-pyridinecarboxaldehyde

Potassium hydroxide

3-Quinuclidinone hydrochloride

→

2-((3-pyridinyl)methylene)-1-azabicyclo[2.2.2]octan-3-one

수율 89.3%

용매

methanol

반응 조건

후처리

1. 1
   기타equipped with a mechanical stirrer
2. 2
   기타resulting in a rise in reaction temperature from 50° C. to 56° C
3. 3
   기타Upon completion of the reaction
4. 4
   여과the reaction mixture was filtered through a sintered glass funnel
5. 5
   세척the filter cake was washed with methanol (74.2 L)
6. 6
   농축The filtrate was concentrated
7. 7
   기타transferred to a reaction flask
8. 8
   workup.ADDITIONwater (66.0 L) was added
9. 9
   workup.STIRRINGThe suspension was stirred for a minimum of 30 min
10. 10
    여과filtered
11. 11
    세척the filter cake was washed with water (90.0 L) until the pH of the rinse
12. 12
    기타The solid was dried under vacuum at 50° C.±5° C. for a minimum of 12 h

실험 절차

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.

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