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

Temperature

0 °C

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.

1. additionTo this solution is then added
2. temperaturewhile maintaining the temperature between -5° and +5° C
3. filtrationThe reaction is filtered
4. extractionthe filter cake extracted with solvent
5. customthe solvents evaporated to dryness
6. dissolutionThe residual N-methyl-L-proline is then dissolved in and
7. customreacted with methanol in the presence of H2SO4
8. temperatureat reflux for 4-24 hr
9. temperatureThe reaction mixture is cooled to 0° C.
10. additionis slowly added to the mixture, until the pH
11. extractionthe title product is extracted from the basic mixture
12. customisolated
13. customafter drying
14. customremoval of the solvent

ORD record

ord-9a28eec084204e05b30a2759811362a7

Source dataset

uspto-grants-1996_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05508418