Triethylamine → 2-[4-(3-Hydroxy-2-sulfobenzoyl)amino-1H-imidazol-1-yl]octanoic acid

HRID 1609762Notes

Reaction equation

HRID 1609762 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([OH:10])[C:5]=1[S:11]([OH:14])(=[O:13])=[O:12])([OH:3])=O.[NH2:15][C:16]1[N:17]=[CH:18][N:19]([CH:21]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:22]([O:24]CC)=[O:23])[CH:20]=1.[N+](C1N=CN(C(CCCCCC)C(OCC)=O)C=1)([O-])=O.C(N(CC)CC)C>C(Cl)(=O)C(Cl)=O.CN(C=O)C.C(O)C.C1COCC1.[Pd].C(OCC)(=O)C>[OH:10][C:6]1[C:5]([S:11]([OH:14])(=[O:13])=[O:12])=[C:4]([CH:9]=[CH:8][CH:7]=1)[C:1]([NH:15][C:16]1[N:17]=[CH:18][N:19]([CH:21]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])[C:22]([OH:24])=[O:23])[CH:20]=1)=[O:3]

Participants

11

Reactant 4

HCID 8471TriethylamineHCID 10062368Ethyl 2-(4-nitro-1H-imidazole-1-yl)octanoateHCID 136691203-Hydroxy-2-sulfobenzoic acidHCID 15222343ethyl 2-(4-amino-1H-imidazol-1-yl)octanoate

Product 1

HCID 152223272-[4-(3-Hydroxy-2-sulfobenzoyl)amino-1H-imidazol-1-yl]octanoic acid

Reagents, catalysts & solvents 6

HCID 6228DimethylformamideCatalystHCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 65578Oxalyl chlorideSolvent

Procedure

2-Carboxy-6-hydroxybenzenesulfonic acid (1.8 mmole, 400 mg) was dissolved in 15 ml of oxalyl chloride. One drop of DMF was added. The reaction was stirred for 30 minutes at room temperature. The solvent was removed in vacuo, and 20 ml THF added. A solution of ethyl 2-(4-amino-1H-imidazol-1-yl)octanoate (prepared by the reduction of 1.8 mmoles of ethyl 2-(4-nitro-1H-imidazol-1-yl)octanoate in ethanol with 5% Pd/C) in 40 ml THF and 2.0 moles of triethylamine was added dropwise. The reaction was stirred at room temperature for 3 hours; ethyl acetate was added. The solution was washed with water, dried over sodium sulfate and concentrated. The intermediate was slurried in ether, filtered, chromatographed over silica gel eluted with 15% methanol in methylene chloride. The ester was hydrolyzed in 20 ml methanol and 45 ml of 2N NaOH at room temperature for 2 hours. The solvent was removed; water was added. The pH was adjusted to 2.0 using 5N HCL. The product was extracted into ethyl acetate, dried over sodium sulfate and concentrated to yield 2-[4-(3-Hydroxy-2-sulfobenzoyl)amino-1H-imidazol-1-yl]octanoic acid. (MS)

Workup

  1. customThe solvent was removed in vacuo, and 20 ml THF
  2. additionadded
  3. stirringThe reaction was stirred at room temperature for 3 hours
  4. washThe solution was washed with water
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. filtrationfiltered
  8. customchromatographed over silica gel
  9. washeluted with 15% methanol in methylene chloride
  10. wait45 ml of 2N NaOH at room temperature for 2 hours
  11. customThe solvent was removed
  12. additionwater was added
  13. extractionThe product was extracted into ethyl acetate
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-9e0a1d08ae1d4a6aa1ed5e2035cb1d2c
Source dataset
uspto-grants-1995_03
Patent number
US05401851

Reaction notes

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