Triethylamine → Tert-butyl (2S)-2-methyl-4-(4-{methyl[(4-oxocyclohexyl)carbonyl]amino}benzyl)piperazine-1-carboxylate

HRID 2370085Notes

Reaction equation

HRID 2370085 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][CH:5]([C:8]([OH:10])=O)[CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.[CH3:17][C@H:18]1[CH2:23][N:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([NH:31][CH3:32])=[CH:27][C:26]=2C)[CH2:21][CH2:20][N:19]1[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35].C(N(CC)CC)C>ClCCl.O.CN(C)C=O>[CH3:17][C@H:18]1[CH2:23][N:22]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([N:31]([CH3:32])[C:8]([CH:5]3[CH2:4][CH2:3][C:2](=[O:1])[CH2:7][CH2:6]3)=[O:10])=[CH:27][CH:26]=2)[CH2:21][CH2:20][N:19]1[C:34]([O:36][C:37]([CH3:38])([CH3:40])[CH3:39])=[O:35]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 1927304-Oxocyclohexanecarboxylic acidHCID 59262129tert-butyl (2S)-2-methyl-4-[2-methyl-4-(methylamino)benzyl]piperazine-1-carboxylate

Product 1

HCID 86700732Tert-butyl (2S)-2-methyl-4-(4-{methyl[(4-oxocyclohexyl)carbonyl]amino}benzyl)piperazine-1-carboxylateYield 32%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-Oxocyclohexanecarboxylic acid (90 mg, 0.633 mmol) was dissolved in dichloromethane (5 mL), and oxalyl chloride (265 μL, 3.16 mmol) and a catalytic amount of dimethylformamide were added thereto at 0° C., and then, the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 30 minutes. The residue obtained by distilling off the solvent in the reaction solution under reduced pressure was dissolved in dichloromethane (15 mL), and tert-butyl (2S)-2-methyl-4-[2-methyl-4-(methylamino)benzyl]piperazine-1-carboxylate (100 mg, 0.313 mmol), which is a known compound, and triethylamine (130 μL, 0.939 mmol) were added thereto at 0° C., and then, the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 1 hour. To the reaction solution, water was added at room temperature, and the organic matter was extracted with dichloromethane. The organic layer was washed with a saturated aqueous solution of sodium chloride and then dried over anhydrous magnesium sulfate and filtered. Then, the solvent was distilled off under reduced pressure, whereby a crude product was obtained. The obtained crude product was purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 0:100 (v/v)), whereby the target compound was obtained as a white solid substance (44.5 mg, yield: 32%).

Workup

  1. customThe residue obtained
  2. distillationby distilling off the solvent in the reaction solution under reduced pressure
  3. dissolutionwas dissolved in dichloromethane (15 mL)
  4. additionwere added
  5. stirringat 0° C., and then, the resulting mixture was stirred under a nitrogen atmosphere at room temperature for 1 hour
  6. extractionthe organic matter was extracted with dichloromethane
  7. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. distillationThen, the solvent was distilled off under reduced pressure, whereby a crude product
  11. customwas obtained
  12. customThe obtained crude product
  13. customwas purified by silica gel column chromatography (hexane:ethyl acetate=100:0 to 0:100 (v/v)), whereby the target compound
  14. customwas obtained as a white solid substance (44.5 mg, yield: 32%)

Sources & evidence

ORD record
ord-26d4fcb14009498293042c220069713c
Source dataset
uspto-grants-2014_04
Patent number
US08710060B2

Reaction notes

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