Cyclobutanone → Tert-butyl 4-cyclobutylpiperazine-1-carboxylate

HRID 574166Notes

Reaction equation

HRID 574166 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:14]1(=O)[CH2:17][CH2:16][CH2:15]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl>[CH:14]1([N:4]2[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]2)[CH2:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 57423951Tert-butyl 4-cyclobutylpiperazine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of compound tert-butyl piperazine-1-carboxylate (37.2 g, 200 mmol) in ClCH2CH2Cl (500 mL) was added cyclobutanone (21 g, 300 mmol) and NaBH(OAc)3 (84.8 g, 400 mmol). The reaction mixture was stirred at rt for 16 h, quenched with saturated aq. Na2CO3 (500 mL) and extracted with DCM (3×500 mL). The combined organic layers were washed with brine (50 mL), dried, filtered and concentrated under reduced pressure to afford the desired compound tert-butyl 4-cyclobutylpiperazine-1-carboxylate (48 g, 100%) [LCMS: Rt=1.67 min, m/z 241.2 (M+H)+].

Workup

  1. customquenched with saturated aq. Na2CO3 (500 mL)
  2. extractionextracted with DCM (3×500 mL)
  3. washThe combined organic layers were washed with brine (50 mL)
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-09f2274ce4bc4703aff7a8fbd5e1d806
Source dataset
uspto-grants-2015_05
Patent number
US09034874B2

Reaction notes

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