Reaction #5162

Reaction equation

Ammonium chloride

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

ethyl chloroformate

ammonium hydroxide

→

title compound

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

Solvents

triethylamine

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   workup.ADDITIONwere added to the mixture at -15° to -20° C.
2. 2
   workup.WAITto stand overnight at room temperature
3. 3
   Extractionwas then extracted with tetrahydrofuran
4. 4
   OtherThe extract was dried
5. 5
   workup.DISTILLATIONfreed from the solvent by distillation under reduced pressure
6. 6
   OtherThe resulting residue was triturated with diethyl ether
7. 7
   Othercrystallization
8. 8
   FiltrationThe crystals were collected by filtration
9. 9
   Washwashed with diethyl ether

Procedure

58 g of (2S, 4R)-1-(t-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid [prepared as described in step (1) aboveπ were dissolved in 850 ml of dry tetrahydrofuran, and then 38.2 ml of triethylamine were added to the mixture at -15° to -20° C. A solution of 26.3 ml of ethyl chloroformate in 240 ml of dry tetrahydrofuran was then added dropwise to the mixture at -15° to -20° C., and the mixture was stirred at the same temperature for 35 minutes. At the end of this time, 258 ml of 28% w/v aqueous ammonium hydroxide were added to the mixture at -15° to -20° C., and the mixture was allowed to stand overnight at room temperature. Ammonium chloride was then added to the reaction mixture, which was then extracted with tetrahydrofuran. The extract was dried and freed from the solvent by distillation under reduced pressure. The resulting residue was triturated with diethyl ether to cause crystallization. The crystals were collected by filtration and washed with diethyl ether to afford 49.7 g of the title compound as colorless crystals, melting at 146°-148° C.

Source