Reaction #2122511

Reaction equation

HCl

octahydrocyclopenta[c]pyrrole

H3PO4

→

(3aS,6aR)-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrole hydrochloride

Solvents

water

water

Conditions

Workup

1. 1
   OtherTo a 3-L 3-neck flask jacketed at 20° C.
2. 2
   Otherto give a colorless, homogeneous solution
3. 3
   workup.ADDITIONwere added
4. 4
   Otherto give a pale yellow solution
5. 5
   Otherwith dry air at approximately 0.2 L/min
6. 6
   TemperatureThe pH of the reaction was maintained at 7.5 via feedback
7. 7
   workup.ADDITIONaddition of the 25 wt % octahydrocyclopenta[c]pyrrole solution in water in 20-100 μL portions
8. 8
   OtherThe dimer of (3aR,6aS) octahydrocyclopenta[c]pyrrole to precipitated from the reaction
9. 9
   workup.ADDITIONAfter 380 mL of the 25 wt % octahydrocyclopenta[c]pyrrole solution in water had been added
10. 10
    Otherthe product was separated from the reaction mixture via steam distillation (still head temperature ˜98° C.)
11. 11
    workup.ADDITIONa suspension of the dimer of (3aS,6aR)-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrole in water

Procedure

To a 3-L 3-neck flask jacketed at 20° C. and stirred at 300 rpm was added 500 mL of dH2O and 20 mL of a 25 wt % octahydrocyclopenta[c]pyrrole solution in water. The pH was adjusted to approximately 7.6 with concentrated H3PO4 to give a colorless, homogeneous solution, to which 2.0 mL of A. niger catalase suspension (Novozyme; “Catalyzyme 101”) and 5.0 g of monoamine oxidase powder of the polypeptide of SEQ ID NO: 16 (prepared by the method of Example 3) were added to give a pale yellow solution. The head space of the vessel was swept with dry air at approximately 0.2 L/min. The pH of the reaction was maintained at 7.5 via feedback controlled addition of the 25 wt % octahydrocyclopenta[c]pyrrole solution in water in 20-100 μL portions. The dimer of (3aR,6aS) octahydrocyclopenta[c]pyrrole to precipitated from the reaction and the reaction mixture became a white slurry. After 380 mL of the 25 wt % octahydrocyclopenta[c]pyrrole solution in water had been added, the product was separated from the reaction mixture via steam distillation (still head temperature ˜98° C.). The receiver pot contained a suspension of the dimer of (3aS,6aR)-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrole in water. 1.1-1.2 equivalent of concentrated HCl was added to the receiver pot break the dimer and give a homogeneous solution of (3aS,6aR)-1,3a,4,5,6,6a-hexahydrocyclopenta[c]pyrrole hydrochloride in water. This solution was used directly to make (1S,3aR,6aS)-octahydrocyclopenta[c]pyrrole-1-carbonitrile in Example 27.

Source