Triethylamine → 1-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamate

HRID 446491Notes

Reaction equation

HRID 446491 reaction equation
[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:20])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][NH:18][CH3:19])[CH2:12][CH2:11]1.C([N:29]([CH2:32][CH3:33])CC)C.BrCC[CH2:37][CH2:38][CH2:39][C:40](Cl)=[O:41].[N-]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl.C(OCC)(=O)C.O1CCCC1.O>[C:1]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:20])[O:9][CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][CH2:17][N:18]([C:40](=[O:41])[CH2:39][CH2:38][CH2:37][CH2:33][CH2:32][NH2:29])[CH3:19])[CH2:12][CH2:11]1

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 898486-Bromohexanoyl chlorideHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate

Product 1

HCID 666715721-{2-[(6-Aminohexanoyl)(methyl)amino]ethyl}piperidin-4-yl biphenyl-2-ylcarbamateYield 75%

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

1-[2-(Methylamino)ethyl]piperidin-4-yl biphenyl-2-ylcarbamate (500 mg, 1.41 mmol) was dissolved in methylene chloride (5 mL), triethylamine (0.236 mL, 1.70 mmol) and 6-bromohexanoyl chloride (0.232 mL, 1.56 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 20 minutes. Water was added to the reaction mixture, the reaction mixture was extracted with ethyl acetate (×3), and the organic layer was washed with saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, then the solvent was evaporated under reduced pressure, the resulting residue was dissolved in N,N-dimethylformamide (3 mL), sodium azide (110 mg, 1.69 mmol) was added, and the mixture was stirred at 60° C. for 5 hours. The reaction mixture was diluted with ethyl acetate, and then the organic layer was washed successively with water (×3) and saturated sodium chloride solution. The organic layer was dried with anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. Triphenylphosphine (555 mg, 2.12 mmol) and water (38 μL, 2.12 mmol) were added to a solution of the resulting residue in tetrahydrofuran (14 mL) under ice cooling, and the mixture was stirred overnight at room temperature. The solvent of the reaction mixture was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→10:1, v/v) to give the title compound (493 mg; yield, 75%) as a yellow oily substance.

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate (×3)
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. dissolutionthe resulting residue was dissolved in N,N-dimethylformamide (3 mL)
  6. stirringthe mixture was stirred at 60° C. for 5 hours
  7. washthe organic layer was washed successively with water (×3) and saturated sodium chloride solution
  8. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. stirringthe mixture was stirred overnight at room temperature
  11. customThe solvent of the reaction mixture was evaporated under reduced pressure
  12. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-7025e82259cd4e7587df0740cb1d34a1
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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