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

HRID 919203Notes

Reaction equation

HRID 919203 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-a9d2c83196a34e4cb066e7c7cbdce995
Source dataset
uspto-grants-2016_03
Patent number
US09273026B2

Reaction notes

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