Dichloromethane → [4-(4-Isobutyryl-piperazine-1-carbonyl)-cyclohexylmethyl]-carbamic acid tert-butyl ester

HRID 538037Notes

Reaction equation

HRID 538037 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C@H:10]1[CH2:15][CH2:14][C@H:13]([C:16]([OH:18])=O)[CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.[C:22]([N:27]1[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]1)(=[O:26])[CH:23]([CH3:25])[CH3:24]>O>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH:10]1[CH2:11][CH2:12][CH:13]([C:16]([N:30]2[CH2:31][CH2:32][N:27]([C:22](=[O:26])[CH:23]([CH3:24])[CH3:25])[CH2:28][CH2:29]2)=[O:18])[CH2:14][CH2:15]1)([CH3:2])([CH3:3])[CH3:4]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 27614092-Methyl-1-(piperazin-1-yl)propan-1-oneHCID 178453624HCID 178453624, compound

Product 1

HCID 67114063[4-(4-Isobutyryl-piperazine-1-carbonyl)-cyclohexylmethyl]-carbamic acid tert-butyl esterYield 80.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of trans-4-(tert-Butoxycarbonylamino-methyl)-cyclohexanecarboxylic acid (8.5 g, 32.8 mmol) in DCM (100 mL) 1,1-carbonyldiimidazole (4.87 g, 30.1 mmol) was added and the reaction was left stirring for 2 hours. Then isobutyryl-piperazine (6.95 g, 27.3 mmol) was also added and the reaction was left stirring for 16 h at room temperature. The mixture was diluted with 50 mL of H2O, the organic phase collected and the solvent removed under reduced pressure. The residue was washed with 1N NaOH solution and the precipitate was filtered, affording 8.7 g (21.9 mmol) of [4-(4-Isobutyryl-piperazine-1-carbonyl)-cyclohexylmethyl]-carbamic acid tert-butyl ester. The product obtained was dissolved in 100 mL of DCM and H2SO4 (2.92 mL, 54.9 mmol) was added. The reaction was stirred for 18 hours and the mixture was washed with 50 mL of 15% NaOH solution, the organic phase was collected and concentrated under reduced pressure. 3.85 g of the titled product were obtained (yield=48%).

Workup

  1. waitthe reaction was left
  2. waitthe reaction was left
  3. stirringstirring for 16 h at room temperature
  4. customthe organic phase collected
  5. customthe solvent removed under reduced pressure
  6. washThe residue was washed with 1N NaOH solution
  7. filtrationthe precipitate was filtered

Sources & evidence

ORD record
ord-d17cb512b72747cb8ce63f46cdf5b15e
Source dataset
uspto-grants-2014_10
Patent number
US08865704B2

Reaction notes

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