Reaction #1379915

Reaction equation

benzyl chloroformate

(3R)-3-hydroxypyrrolidine

triethylamine

→

title compound

Benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Solvents

dichloromethane

dichloromethane

ethyl acetate hexane

Conditions

Workup

1. 1
   workup.ADDITIONthermocouple, addition funnel
2. 2
   Otherthe reaction temperature below 20° C
3. 3
   Otherthe bath was removed
4. 4
   Temperatureto warm to ambient temperature overnight
5. 5
   workup.ADDITIONThe mixture was poured into a large extractor
6. 6
   workup.ADDITIONcontaining approximately 15 L of saturated aqueous sodium bicarbonate solution
7. 7
   ExtractionThe aqueous phase was back-extracted with two 2-L portions of dichloromethane
8. 8
   DryingThe combined organics were-dried over magnesium sulfate
9. 9
   Concentrationconcentrated
10. 10
    Otherto give an orange oil
11. 11
    Washeluted sequentially with 8 L of 50%, 16 L of 75%

Procedure

A 22-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 425 g (4.88 mol) of (3R)-3-hydroxypyrrolidine, 8 L of dichloromethane, and 1 L (7.17 mol) of triethylamine. The solution was cooled to 5-10° C. with an ice bath and then 1000 g (5.86 mol) of benzyl chloroformate was added dropwise over a period of about 1.5 h keeping the reaction temperature below 20° C. The reaction mixture was stirred for an additional hour in the ice bath, then the bath was removed and the reaction mixture was allowed to warm to ambient temperature overnight. The mixture was poured into a large extractor containing approximately 15 L of saturated aqueous sodium bicarbonate solution. The aqueous phase was back-extracted with two 2-L portions of dichloromethane. The combined organics were-dried over magnesium sulfate and concentrated to give an orange oil. The crude material was taken up in dichloromethane, applied to a 5-kg column of silica gel prepacked in 50% ethyl acetate/hexane, and eluted sequentially with 8 L of 50%, 16 L of 75%, then 100% ethyl acetate/hexane to provide the title compound as a yellow oil which crystallized upon standing.

Source