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

HRID 1192612Notes

Reaction equation

HRID 1192612 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.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C.O1CCCC1>[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

6

Reactant 3

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

Product 1

HCID 57423951Tert-butyl 4-cyclobutylpiperazine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of tert-butyl piperazine-1-carboxylate (0.72 g, 0.0039 mol) and cyclobutanone (0.87 mL, 0.012 mol) in acetonitrile (10 mL) and tetrahydrofuran (10 mL) was added sodium triacetoxyborohydride (2.4 g, 0.012 mol). The resulting mixture was stirred at room temperature for 4 hours. The reaction was quenched with aq. NaHCO3 solution and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated to give tert-butyl 4-cyclobutylpiperazine-1-carboxylate, which was treated with 4.57 M hydrogen chloride in 1,4-dioxane (10 mL, 0.04 mol) at room temperature for 2 hours and then evaporated to dryness to give the desired product. LCMS calculated for C8H17N2 (M+H)+: m/z=141.1; Found: 141.2

Workup

  1. customThe reaction was quenched with aq. NaHCO3 solution
  2. extractionextracted with dichloromethane
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-6b6c680f8d6146c986de4ae8fafc2195
Source dataset
uspto-grants-2014_03
Patent number
US08680108B2

Reaction notes

Loading…