Difluoromethyl-containing diethyl 1,2,3,4-tetrahydropyridine-3,5-dicarboxylate derivatives were synthesized in up to 90% yields by the Mannich reaction of ethyl 4,4-difluoroacetoacetate with formaldehyde and primary amine hydrochlorides. The effects of the reactant structure and reaction conditionson the efficiency of formation of 1,2,3,4-tetrahydropyridines and hexahydropyrimidines was studied. In the presence of NaCl in an acetate buffer (рН 4), the 1,2,3,4-tetrahydropyridine structure is formed selectively. When 4-aminophenol hydrochloride is used, the 3,4,5,6-tetrahydropyrimidin-1-ium difluoroacetate salt is produced, apart from the target product. The reactions with (S)-α-amino acid ester hydrochlorides afford mixtures of two diastereomeric 1,2,3,4-tetrahydropyridines.

通过 4,4-二氟乙酰乙酸乙酯与甲醛和伯胺盐酸盐的曼尼希反应，合成了含二氟甲基的 1,2,3,4-四氢吡啶-3,5-二羧酸二乙酯衍生物，收率高达 90%。研究了反应物结构和反应条件对1,2,3,4-四氢吡啶和六氢嘧啶生成效率的影响。在醋酸盐缓冲液 (рН 4) 中存在 NaCl 时，会选择性地形成 1,2,3,4-四氢吡啶结构。使用4-氨基苯酚盐酸盐时，除目标产物外，还生成3,4,5,6-四氢嘧啶-1-鎓二氟乙酸盐。与 ( S )-α-氨基酸酯盐酸盐反应得到两种非对映体 1,2,3,4-四氢吡啶的混合物。