Reaction #1379916

Reaction equation

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

(diethylamino)sulfur trifluoride

water

sodium bicarbonate

→

title compound

Benzyl (3S)-3-fluoropyrrolidine-1-carboxylate

Solvents

dichloromethane

dichloromethane

Conditions

Workup

1. 1
   workup.ADDITIONthermocouple, addition funnel
2. 2
   Otherthe reaction temperature below −70° C
3. 3
   Temperaturewarm slowly to ambient temperature overnight
4. 4
   workup.ADDITIONThe reaction mixture was added portion-wise with caution to a large extractor
5. 5
   ExtractionThe mixture was extracted with 8 L of ethyl acetate
6. 6
   WashThe organic layer was washed with saturated aqueous brine
7. 7
   Dryingdried over magnesium sulfate
8. 8
   Concentrationconcentrated
9. 9
   Otherto give a brown oil
10. 10
    OtherPurification by flash chromatography (silica gel
11. 11
    Washeluting with a 10 to 30% ethyl acetate/hexane gradient)

Procedure

A 5-L, 3-neck, round bottom flask equipped with mechanical stirrer, thermocouple, addition funnel and nitrogen bubbler was charged with 375 mL (2.84 mol) of (diethylamino)sulfur trifluoride and 400 mL of dichloromethane. The solution was cooled to −78° C. To this was added via addition funnel a solution of 304 g (1.37 mol) of benzyl (3R)-3-hydroxypyrrolidine-1-carboxylate in 400 mL of dichloromethane over a 2-h period keeping the reaction temperature below −70° C. The reaction mixture was allowed to stir and warm slowly to ambient temperature overnight. The reaction mixture was added portion-wise with caution to a large extractor containing ice, water, and saturated aqueous sodium bicarbonate solution. The mixture was extracted with 8 L of ethyl acetate. The organic layer was washed with saturated aqueous brine, dried over magnesium sulfate, and concentrated to give a brown oil. Purification by flash chromatography (silica gel, eluting with a 10 to 30% ethyl acetate/hexane gradient) gave the title compound as a brown oil.

Source