Piperazine → tert-Butyl 3-(piperazin-1-yl)azetidine-1-carboxylate

HRID 1457089Notes

Reaction equation

HRID 1457089 reaction equation
[NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16](OS(C)(=O)=O)[CH2:15]1)=[O:13])([CH3:10])([CH3:9])[CH3:8]>>[C:7]([O:11][C:12]([N:14]1[CH2:17][CH:16]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)[CH2:15]1)=[O:13])([CH3:10])([CH3:8])[CH3:9]

Participants

3

Reactant 2

HCID 4837PiperazineHCID 10753243Tert-butyl 3-(methanesulfonyloxy)azetidine-1-carboxylate

Product 1

HCID 19360775tert-Butyl 3-(piperazin-1-yl)azetidine-1-carboxylate

Conditions

Temperature
120 °C

Procedure

Piperazine (23.69 g, 8 mol equivalent) was melted and 1-(t-butoxycarbonyl)-3-methanesulphonyloxyazetidine (see International Patent Application Publication no WO93/19059; 8.64 g, 34.4 mmol) added. The mixture was heated at 120° C. for 15 hours under nitrogen. The reaction was cooled to room temperature and the excess piperazine removed under reduced pressure. The residue was chromatographed on silica gel using gradient elution (methanol:dichloromethane 1:19 changing to 1:4, by volume) to give the title compound (6.32 g). LRMS m/z=242 (m+1)+. 1H-NMR (d6 -DMSO): δ=1.35(s,9H), 2.4-2.5(m,4H), 3.0-3.1 (m,5H), 3.2-4.2(m,br.,5H)ppm.

Workup

  1. addition8.64 g, 34.4 mmol) added
  2. temperatureThe reaction was cooled to room temperature
  3. customthe excess piperazine removed under reduced pressure
  4. customThe residue was chromatographed on silica gel using gradient elution (methanol:dichloromethane 1:19 changing to 1:4, by volume)

Sources & evidence

ORD record
ord-f3c761d5286245ee8a65015c05467684
Source dataset
uspto-grants-1998_12
Patent number
US05846965

Reaction notes

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