Trifluoroacetic acid → HCID 86753679, compound

HRID 361765Notes

Reaction equation

HRID 361765 reaction equation
[CH2:1]([O:3][C:4](=[O:28])[CH2:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:27])[C:13]([CH3:26])([CH3:25])[CH:14]([CH2:23][CH3:24])[NH:15][C:16](OC(C)(C)C)=[O:17])[CH2:8][CH2:7]1)[CH3:2].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O.[N:44]1([C:50]([C:52]2[CH:60]=[CH:59][C:55](C(O)=O)=[CH:54][CH:53]=2)=[NH:51])[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1.C1C=CC2N(O)N=NC=2C=1>C(N(CC)CC)C>[N:44]1([C:50]([C:52]2[CH:53]=[CH:54][C:55]([C:16]([NH:15][CH:14]([CH2:23][CH3:24])[C:13]([CH3:25])([CH3:26])[C:12]([N:9]3[CH2:10][CH2:11][CH:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:28])[CH2:7][CH2:8]3)=[O:27])=[O:17])=[CH:59][CH:60]=2)=[NH:51])[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 757711-HydroxybenzotriazoleHCID 54382588HCID 54382588, compoundHCID 85161906HCID 85161906, compound

Product 1

HCID 86753679HCID 86753679, compoundYield 22.1%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To the obtained N-(N-Boc-βethyl-α,α-dimethyl-β-alanyl)-4-piperidineacetic acid ethyl ester (0.38 g, 0.95 mmol) were added anisole (0.3 ml) and TFA (10 ml) and the mixture was stirred for 1 hour under cooling with ice. After the TFA was distilled off at room temperature, the residue was washed with hexane 3 times and dissolved in DMF (20 ml) under cooling with ice. After the resulting solution was neutralized with triethylamine, 4-(4-morpholinoimidoyl)benzoic acid (0.25 g, 1.05 mmol), HOBT (0.14 g, 1.05 mmol) and WSDC (0.22 g, 1.14 mmol) were added thereto and the mixture was stirred overnight. After the solvent was distilled off, the residue was dissolved in ethyl acetate, washed sequentially with a 5% aqueous solution of citric acid, a 5% aqueous solution of sodium hydrogencarbonate and saturated saline 3 times each, and dried over anhydrous sodium sulfate. After the solvent was distilled off, the residue was applied to a silica gel column (2.1 φ×20 cm) and eluted with a mixed solution (chloroform:ethanol=30:1). The desired fractions were collected and the solvents were distilled off to yield a powder of the titled compound (108 mg, 22%).

Workup

  1. temperatureunder cooling with ice
  2. distillationAfter the TFA was distilled off at room temperature
  3. washthe residue was washed with hexane 3 times
  4. dissolutiondissolved in DMF (20 ml)
  5. temperatureunder cooling with ice
  6. additionwere added
  7. stirringthe mixture was stirred overnight
  8. distillationAfter the solvent was distilled off
  9. dissolutionthe residue was dissolved in ethyl acetate
  10. washwashed sequentially with a 5% aqueous solution of citric acid
  11. dry with materiala 5% aqueous solution of sodium hydrogencarbonate and saturated saline 3 times each, and dried over anhydrous sodium sulfate
  12. distillationAfter the solvent was distilled off
  13. washeluted with a mixed solution (chloroform:ethanol=30:1)
  14. customThe desired fractions were collected
  15. distillationthe solvents were distilled off

Sources & evidence

ORD record
ord-fb9ba2793ca24c25adf63e579c8c2290
Source dataset
uspto-grants-1999_02
Patent number
US05866592

Reaction notes

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