Methyl iodide → Ethyl trans-4-azido-3-methoxy-1-piperidinecarboxylate

Participants

Reaction Steps

To a stirred solution of 20.6 parts of 2-methyl-2-propanol, potassium salt in 54 parts of N,N-dimethylformamide was added dropwise a solution of 30.3 parts of a mixture of ethyl trans-4-azido-3-hydroxy-1-piperidinecarboxylate and ethyl trans-3-azido-4-hydroxy-1-piperidinecarboxylate in 45 parts of N,N-dimethylformamide at a temperature below 20° C. (ice bath). Upon completion, stirring was continued for 1 hour at room temperature. 25.9 parts of iodomethane were added dropwise at a temperature <10° C. Upon completion, stirring was continued overnight at room temperature. The reaction mixture was poured into 400 parts of water. The product was extracted with trichloromethane. The extract was washed with a sodium chloride solution, dried, filtered and evaporated in vacuo. The residue was purified by column chromatography over silica gel using trichloromethane as eluent. The desired fractions were collected and the eluent was evaporated, yielding 15.6 parts (48.8%) of ethyl trans-4-azido-3-methoxy-1-piperidinecarboxylate as a residue (interm. 4).

Provenance & Evidence