Trifluoroacetic acid → HCID 66671673, compound

HRID 446528Notes

Reaction equation

HRID 446528 reaction equation
[C:1]([O:5][C:6]([N:8]([CH3:35])[CH2:9][CH2:10][CH2:11][N:12]([CH3:34])[C:13]([C:15]1[CH:20]=[CH:19][C:18]([NH:21][CH2:22][CH2:23][O:24][CH2:25][CH2:26][C:27](OC(C)(C)C)=[O:28])=[CH:17][CH:16]=1)=[O:14])=[O:7])([CH3:4])([CH3:3])[CH3:2].FC(F)(F)C(O)=O.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.C(Cl)(=O)C(C)(C)C.[C:72]1([C:92]2[CH:97]=[CH:96][CH:95]=[CH:94][CH:93]=2)[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[NH:78][C:79](=[O:91])[O:80][CH:81]1[CH2:86][CH2:85][N:84]([CH2:87][CH2:88][NH:89][CH3:90])[CH2:83][CH2:82]1>C(Cl)Cl>[C:72]1([C:92]2[CH:97]=[CH:96][CH:95]=[CH:94][CH:93]=2)[CH:77]=[CH:76][CH:75]=[CH:74][C:73]=1[NH:78][C:79](=[O:91])[O:80][CH:81]1[CH2:86][CH2:85][N:84]([CH2:87][CH2:88][N:89]([C:27](=[O:28])[CH2:26][CH2:25][O:24][CH2:23][CH2:22][NH:21][C:18]2[CH:19]=[CH:20][C:15]([C:13](=[O:14])[N:12]([CH2:11][CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:35])[CH3:34])=[CH:16][CH:17]=2)[CH3:90])[CH2:83][CH2:82]1

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 62493Pivaloyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 566436031-(2-(Methylamino)ethyl)piperidin-4-yl [1,1'-biphenyl]-2-ylcarbamateHCID 86663437HCID 86663437, compound

Product 1

HCID 66671673HCID 66671673, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The compound (188 mg, 0.381 mmol) obtained in Example 28e was dissolved in methylene chloride (4 mL), trifluoroacetic acid (2 mL) was added under ice cooling, and the mixture was stirred at room temperature for 2.5 hours. The solvent was evaporated under reduced pressure, and moisture was removed from the resulting residue azeotropically with toluene (×2). The resulting residue was dissolved in methylene chloride (4 mL), triethylamine (0.318 mL, 2.29 mmol) and di-tert-butyl dicarbonate (183 mg, 0.838 mmol) were added, and the mixture was stirred at room temperature for 18.5 hours. The solvent was evaporated under reduced pressure, the resulting residue was dissolved in methylene chloride (4 mL), triethylamine (79 μL, 0.572 mmol) and pivaloyl chloride (49 μL, 0.400 mmol) were added under ice cooling, and the mixture was stirred at room temperature for 20 minutes. 1-[2-(Methylamino)ethyl]piperidin-4-yl biphenyl-2-ylcarbamate (296 mg, 0.838 mmol) was added under ice cooling, and the mixture was stirred at room temperature for 2 hours. The solvent was evaporated under reduced pressure, and the resulting residue was purified by NH silica gel column chromatography (ethyl acetate:methanol=50:1, v/v) to give the title compound (196 mg; yield, 66%) as a white solid.

Workup

  1. customThe solvent was evaporated under reduced pressure, and moisture
  2. customwas removed from the resulting residue azeotropically with toluene (×2)
  3. dissolutionThe resulting residue was dissolved in methylene chloride (4 mL)
  4. stirringthe mixture was stirred at room temperature for 18.5 hours
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe resulting residue was dissolved in methylene chloride (4 mL)
  7. stirringthe mixture was stirred at room temperature for 20 minutes
  8. stirringthe mixture was stirred at room temperature for 2 hours
  9. customThe solvent was evaporated under reduced pressure
  10. customthe resulting residue was purified by NH silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-896c9e11361f4e5397fcc0039f5f0811
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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