Cyclobutanone → tert-butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]-4-cyclobutylpiperazine-1-carboxylate

HRID 603194Notes

Reaction equation

HRID 603194 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C@H:16]2[CH2:21][NH:20][CH2:19][CH2:18][N:17]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[C:38]1(=O)[CH2:41][CH2:40][CH2:39]1.S([O-])([O-])(=O)=O.[Mg+2].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][N:11]([C:14]([C@H:16]2[CH2:21][N:20]([CH:38]3[CH2:41][CH2:40][CH2:39]3)[CH2:19][CH2:18][N:17]2[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[O:15])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 14496CyclobutanoneHCID 24083Sulfuric acid magnesium salt (1:1)HCID 81531DiisopropylethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 57656790tert-Butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]piperazine-1-carboxylate

Product 1

HCID 57656643tert-butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]-4-cyclobutylpiperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]piperazine-1-carboxylate (4.5 g) was dissolved in tetrahydrofuran (300 ml) and stirred at room temperature. N,N-Diisopropylethylamine (5.95 ml) was added followed by cyclobutanone (3.25 g) and magnesium sulphate (300 mg). After 45 minutes, sodium triacetoxyborohydride (9.78 g) was added and stirring continued overnight. Inorganic residues were removed by filtration and the filtrate concentrated in vacuo. The residue was purified by chromatography eluting with 0-10% methanol/dichloromethane. This gave tert-butyl (2R)-2-[(4-benzylpiperazin-1-yl)carbonyl]-4-cyclobutylpiperazine-1-carboxylate as a colourless gum (5.12 g).

Workup

  1. stirringstirring continued overnight
  2. customInorganic residues were removed by filtration
  3. concentrationthe filtrate concentrated in vacuo
  4. customThe residue was purified by chromatography
  5. washeluting with 0-10% methanol/dichloromethane

Sources & evidence

ORD record
ord-3bce16e8f2734f478778ecfdc2855cc5
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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