Methyl iodide → Ethyl 3,4,4-trimethoxypiperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a stirred mixture of 35 parts of ethyl 3-hydroxy-4,4-dimethoxy-1-piperidinecarboxylate and 144 parts of N,N-dimethylformamide were added portionwise 8.2 parts of sodium hydride dispersion 50%: exothermic reaction (temp. roses to 30° C.; cooling in a water-bath was necessary to keep the temperature below 30° C.). The whole was stirred for 1.50 hours at about 30° C. and then it is cooled to room temperature. 24.1 Parts of iodomethane were added dropwise (strong exothermic reaction) while the temperature was kept below 30° C. Upon completion, stirring was continued over week-end at room temperature. The reaction mixture was poured onto water and the product was extracted with 4-methyl-2-pentanone. The extract was washed with water, dried, filtered and evaporated, yielding 35.9 parts (95.7%) of ethyl 3,4,4-trimethoxy-1-piperidinecarboxylate as an oily residue (intermediate 64).

Provenance & Evidence