Reaction #5173

Reaction equation

hydrochloric acid

(2S, 4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid

ethyl chloroformate

dimethylamine

→

title compound

(2S, 4R)-1-(t-Butoxycarbonyl)-2-(N,N-dimethylcarbamoyl)-4-hydroxypyrrolidine

Solvents

tetrahydrofuran

triethylamine

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGThe mixture was then stirred for 3 hours under ice cooling
2. 2
   workup.WAITto stand overnight at room temperature
3. 3
   Extractionextracted with ethyl acetate
4. 4
   WashThe extract was washed with an aqueous solution of sodium chloride
5. 5
   Otherdried
6. 6
   OtherThe solvent was then removed by distillation under reduced pressure
7. 7
   Otherthe residue was purified by column chromatography through silica gel (
8. 8
   Washeluted with a 9:1 by volume mixture of ethyl acetate and methanol)

Procedure

3.84 ml of triethylamine was added, at -15° to -20° C., to a solution of 5.8 g of (2S, 4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid dissolved in 85 ml of dry tetrahydrofuran, and then a solution of 2.63 ml of ethyl chloroformate in 25 ml of dry tetrahydrofuran was added to the resulting mixture at the same temperature. The reaction mixture was then stirred for 2 hours, after which 19.75 ml of 50% by volume aqueous dimethylamine was added to it at -20° to -25° C. The mixture was then stirred for 3 hours under ice cooling, after which is was allowed to stand overnight at room temperature. At the end of this time, the mixture was poured into a mixture of 30 ml of concentrated hydrochloric acid and ice and extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried. The solvent was then removed by distillation under reduced pressure, and the residue was purified by column chromatography through silica gel (eluted with a 9:1 by volume mixture of ethyl acetate and methanol) to afford 429 mg of the title compound.

Source