Sodium Hydroxide → 2-(2-Chlorophenyl)-4-(piperidin-1-yl)butanenitrile

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A reaction vessel under a nitrogen atmosphere containing 74.0 kg of 1-(2-chloroethyl)piperidine, monohydrochloride at 10° C. was charged with 255.4 kg of sodium hydroxide solution (50% w/w). The reaction was warmed to 30° to 35° C. and 67.0 kg of 2-chlorobenzeneacetonitrile and 1.4 kg of methyltributylammonium chloride (75% w/w in water) were added. The reaction was stirred at 40° C. for 6 h and then heated to 60° C. for at least 6 h. When the reaction was completed as indicated by gas chromatographic analysis, the reaction mixture was cooled to 25° C. The reaction mixture was diluted with 335 L of water and 134 L of toluene and stirred for 30 min. After separation of the layers, the organic phase was extracted with 275 L of hydrochloric acid (2N). The acidic extract was washed twice with 50 L of toluene, basified with 30 L of sodium hydroxide solution (50% w/w) to a pH>12 and extracted twice with a total of 368 L of heptane. The combined organic phase was washed with 50 L of water and filtered through a layer of diatomaceous earth. The filtrate was dried by azeotropic distillation. The solvent was removed by distillation under reduced pressure to give 104.5 kg (90.0%) of the title product α-(2-chlorophenyl)-1-piperidinebutanenitrile as an oil. Analysis calcd for C15H19ClN2 : C,68.56; H,7.29; Cl,13.49; N,10.66. Found: C,69.64; H,7.53; Cl,12.45; N,9.75. The crude product (oil) was carried forward to the next step without purification. The purity of the title compound was estimated to be 98% based on GC Method B.

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