Case Study

Target Molecule: L10295, (R)-(-)-3-Fluoropyrrolidine hydrochloride

Initially made from (S)-3-Hydroxypyrrolidine hydrochloride using 3 stage route; Protection, fluorination with DAST followed by deprotection.


  • 3 stage route, previously performed on <1kg scale with low overall yield ~20%
  • Expensive fluorinating reagent
  • Not economically viable at plant scale, new requirement was for 100kg
  • No developed chiral hplc method. Optical rotation previously used as basis for chiral purity


  •  new one-pot process was developed from the same raw material
  • DAST was replaced with SF4, so much lower cost
  • Yield increased to ~50%
  • Formation of new impurity (3-chlropyrrolidine.HCl) was seen at ~0.2%
  • Recrystallisation method developed to remove this impurity
  • 100kg produced at competitive price. 1/3rd price of original route, scale for scale.
  • Improved chiral hplc method developed. 98% e.e
  • New one-pot route now allows scale-up to multi-tonne quantities