Reaction #5167

Reaction equation

sodium chloride

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

ethyl chloroformate

methylamine

→

title compound

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

Solvents

tetrahydrofuran

triethylamine

tetrahydrofuran

Conditions

Workup

1. 1
   Otherto rise to room temperature
2. 2
   workup.WAITto continue for 1 hour
3. 3
   Extractionextracted thrice with ethyl acetate
4. 4
   WashThe combined extracts were washed with an aqueous solution of sodium chloride
5. 5
   Dryingdried over anhydrous magnesium sulfate
6. 6
   OtherThe solvent was then removed by distillation under reduced pressure

Procedure

9.91 ml of triethylamine were added at -40° C. to a solution of 15.03 g of (2S, 4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid dissolved in 250 ml of dry tetrahydrofuran, and then a solution of 6.81 ml of ethyl chloroformate in 30 ml of dry tetrahydrofuran was added at -30° to -40° C. to the resulting mixture, which was then stirred at the same temperature for 1 hour, 16.82 ml of a 40% by volume aqueous methylamine solution were then added at -30° C., and the temperature of the reaction mixture was allowed to rise to room temperature; the reaction was then allowed to continue for 1 hour. At the end of this time, the reaction mixture was mixed with a small amount of an aqueous solution of sodium chloride and extracted thrice with ethyl acetate. The combined extracts were washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under reduced pressure, giving 12.76 g of the title compound as a colorless oil.

Source