Triethylamine → HCID 66671698, compound

HRID 446503Notes

Reaction equation

HRID 446503 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(CC)CC)C.Br[CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][C:40](Cl)=[O:41].C([O-])(=[O:45])C.[K+].C1OCCOCCOCCOCCOCCOC1.C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.O.[Cl-].[Na+].CO>[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:35](=[O:45])[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][OH:41])[CH3:19])[CH2:12][CH2:11]1

Participants

11

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 2855718-Crown-6HCID 898486-Bromohexanoyl chlorideHCID 517044Potassium AcetateHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamate

Product 1

HCID 66671698HCID 66671698, compoundYield 90%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-[2-(Methylamino)ethyl]piperidin-4-yl biphenyl-2-ylcarbamate (5.00 g, 14.1 mmol) was dissolved in methylene chloride (141 mL), triethylamine (2.35 mL, 16.9 mmol) and 6-bromohexanoyl chloride (2.32 mL, 15.6 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 20 minutes. The solvent was evaporated under reduced pressure, water was added to the resulting residue, the 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, the solvent was evaporated under reduced pressure, the resulting residue was dissolved in N,N-dimethylformamide (47 mL), potassium acetate (2.08 g, 21.2 mmol) and 18-crown-6 (373 mg, 1.41 mmol) were added, and the mixture was stirred at 60° C. for 15.5 hours. Methanol (47 mL) and potassium carbonate (5.85 g, 42.3 mmol) were added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours. The mixture was diluted with methylene chloride, water and saturated sodium chloride solution were added, and the mixture was extracted with methylene chloride (×3). The organic layer was dried with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=100:0→20:1, v/v) to give the title compound (5.93 g; yield, 90%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure, water
  2. additionwas added to the resulting residue
  3. extractionthe mixture was extracted with ethyl acetate (×3)
  4. washthe organic layer was washed with saturated sodium chloride solution
  5. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. dissolutionthe resulting residue was dissolved in N,N-dimethylformamide (47 mL)
  8. stirringthe mixture was stirred at 60° C. for 15.5 hours
  9. stirringthe mixture was stirred at room temperature for 2 hours
  10. additionwere added
  11. extractionthe mixture was extracted with methylene chloride (×3)
  12. dry with materialThe organic layer was dried with anhydrous sodium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-10587542f02c4e0cb1a2a0d2e437b093
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

Loading…