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The multicomponent reaction of aldehydes, cyano-containing C-H acids, esters of 3-oxocarboxylic acid and ammonium acetate led to unexpected results. The boiling of starting materials in methanol for one to two hours resulted in the formation of polysubstituted 1,4,5,6-tetrahydropyridines with two or three stereogenic centers. During the 2020 lockdown, we obtained key intermediates of this six-step domino reaction. A number of fast and slow reactions occurred during the prolonged stirring of the reaction mass at rt. Sequence: 1. Knoevenagel condensation; 2. Michael addition; 3. Mannich reaction; 4. cyclization—fast reactions and cyclization of the product polysubstituted 2-hydroxypiperidine—was isolated after 40 min stirring at rt. Further monitoring proved the slow dehydration of 2-hydroxypiperidine to obtain 3,4,5,6-tetrahydropyridine after 7 days. Then, four-month isomerization occurred with 1,4,5,6-tetrahydropyridine formation. All reactions were stereoselective. Key intermediates and products structures were verified by X-ray diffraction analysis. Additionally, we specified conditions for the selective intermediates’ preparation.