Hydrochloric Acid → 1-[6-Chloro-2-(trifluoromethyl)-4-piperidinylmethyl]-2-pyrrolidinone

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Reaction Steps

To a solution of 1-(4-pyridinylmethyl)-2-pyrrolidinone (Intermediate compound IV, 905 g, 5.14 moles) in potable water (11 L) was added reagent grade hydrochloric acid (470 mL, about 5.65 moles) and platinum IV oxide (25 g). The stirred mixture was treated with hydrogen at low pressure (5 inches of water pressure) and after hydrogen uptake was complete (about 3 days) the catalyst was removed by filtration and sodium hydroxide (50% solution, 130 g, 14.1 moles) was added. Next acetonitrile (1.68 L) was added and the solution was cooled to 25° while rapidly stirring and 5.14 moles of 4,6-dichloro-2-trifluoromethylpyrimidine, V, was added dropwise over a period of about 2 hours. The temperature is generally held at or below 25° during this addition. The product separates during this addition or on continued stirring overnight and can be removed by filtration.

Provenance & Evidence