Acetic Acid → Tert-butyl 4-cyclobutylpiperazine-1-carboxylate

HRID 1437238Notes

Reaction equation

HRID 1437238 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:14]1(=O)[CH2:17][CH2:16][CH2:15]1.C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH:14]2[CH2:17][CH2:16][CH2:15]2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 14496CyclobutanoneHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5003444Sodium cyanoborohydride

Product 1

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

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Piperazine-4-carboxylic acid tert-butyl ester (3.74 g), cyclobutanone (3.00 mL), and acetic acid (1.15 mL) were dissolved in methanol (100 mL). To the resultant solution, sodium cyanoborohydride (1.89 g) was added at room temperature, followed by stirring for 3 hours. The solvent was evaporated under reduced pressure, and the residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate. The organic layer was washed with saturated brine, and then dried over magnesium sulfate anhydrate, followed by filtration. The solvent was evaporated under reduced pressure. The residue was purified through silica gel column chromatography (chloroform-methanol), to thereby give the title compound as an oily product (4.43 g, 92%).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. customthe residue was partitioned by use of ethyl acetate and saturated aqueous sodium hydrogencarbonate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over magnesium sulfate anhydrate
  5. filtrationfollowed by filtration
  6. customThe solvent was evaporated under reduced pressure
  7. customThe residue was purified through silica gel column chromatography (chloroform-methanol)

Sources & evidence

ORD record
ord-6f8060a80d81494d93d4431d6c9c2cc9
Source dataset
uspto-grants-2009_11
Patent number
US07622471B2

Reaction notes

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