Formaldehyde → (S)-Methyl 1-methylpyrrolidine-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

The L-proline is dissolved in methanol, the solution is cooled to 0° C. and 36% aqueous formaldehyde is added with stirring. To this solution is then added powdered NaBH4 in portions while maintaining the temperature between -5° and +5° C. The reaction is filtered, the filter cake extracted with solvent and combined with the filtrate, and the solvents evaporated to dryness. The residual N-methyl-L-proline is then dissolved in and reacted with methanol in the presence of H2SO4 at reflux for 4-24 hr. The reaction mixture is cooled to 0° C., and with vigorous stirring a solution of K2CO3 is slowly added to the mixture, until the pH is between pH 7 and 8, then the title product is extracted from the basic mixture and isolated after drying and removal of the solvent.

Provenance & Evidence