Ethyl Acetate → Niguldipine hydrochloride, (+/-)-

Beteiligte Stoffe

Reaktionsschritte

86.6 g of 3-methyl 5-(3-bromopropyl) (-)-1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-pyridine-3,5-dicarboxylate, 50 g of 4,4-diphenylpiperidine hydrochloride and 69 g of finely milled potassium carbonate are heated together in 300 ml of dimethylformamide for 5 h at 100° C. with vigorous stirring and under a nitrogen atmosphere. After cooling, 500 ml of ethyl acetate and 1 l of water are added in succession and the mixture is stirred thoroughly. After phase separation, the organic phase is washed 4 times with water, dried over sodium sulphate and evaporated in vacuo. The residue is dissolved in 1 l of dioxane and 15.2 ml of concentrated hydrochloric acid solution (12.5 M, d=1.19) are added to the cooled solution; about 200 ml of the solvent mixture are then distilled off in vacuo. On standing at room temperature, the product crystallises spontaneously or after seeding or trituration; it is filtered off under suction after 16 h, washed with dioxane and diisopropyl ether and dried in vacuo at 80°-100° C. For purification, the product is dissolved in dichloromethane. After the addition of 800 ml of dioxane, the dichloromethane is distilled off again. The product which has crystallised out after seeding and standing at room temperature for 16 hours is filtered off under suction, washed with dioxane and diisopropyl ether and dried at 100° C. 97 g of the title compound of m.p. 158°-160° C. and [α]22 436 =-39° (c=1, methanol) or [α]22D =-14.4° (c=1. methanol) are obtained.

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