Trifluoroacetic acid → 1-(Oxetan-3-yl)piperazine

HRID 633403Notes

Reaction equation

HRID 633403 reaction equation
FC(F)(F)C(O)=O.[O:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]2)[CH2:9]1>C(Cl)Cl>[O:8]1[CH2:11][CH:10]([N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)[CH2:9]1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59605443Tert-butyl 4-(oxetan-3-YL)piperazine-1-carboxylate

Product 1

HCID 574162871-(Oxetan-3-yl)piperazineYield 98%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (100 mL, 33.0 eq, 1327.9 mmol) was added to a solution of tert-butyl 4-(oxetan-3-yl)piperazine-1-carboxylate (9.8 g, 1.0 eq, 40.2 mmol) in CH2Cl2 (500 mL). Reaction mixture was allowed to stir at room temperature. Progress of the reaction was monitored by TLC analysis. After 30 minutes the reaction mixture was concentrated on a rotovap (bath temperature was maintained at 20° C.) to remove the volatiles. The crude solution was loaded on to SCX-2 (100 g, obtained from Sillicycle) and eluted with CH2Cl2/MeOH [1:1 CH2Cl2/MeOH (100 mL) & then with neat MeOH (100 mL)]. Then the product was eluted with 2M NH3 in MeOH (200 mL). Fractions eluted with 2M NH3 in MeOH were combined and concentrated under reduced pressure to leave 1-(oxetan-3-yl)piperazine as a colourless oil in 98% yield.

Workup

  1. customReaction mixture
  2. concentrationAfter 30 minutes the reaction mixture was concentrated on a rotovap (bath temperature was maintained at 20° C.)
  3. customto remove the volatiles
  4. washeluted with CH2Cl2/MeOH [1:1 CH2Cl2/MeOH (100 mL)
  5. washThen the product was eluted with 2M NH3 in MeOH (200 mL)
  6. washFractions eluted with 2M NH3 in MeOH
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4c0da1d5e32a4ef1a39e3cc3e5b14c16
Source dataset
uspto-grants-2016_04
Patent number
US09321763B2

Reaction notes

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