Dicyclohexylcarbodiimide → 2-[4-[2-(2H-tetrazol-5-yl)benzamido]-1H-benzimidazol-1-yl]octanoic acid

HRID 1938603Notes

Reaction equation

HRID 1938603 reaction equation
[N+:1]([C:4]1[C:12]2[N:11]=[CH:10][N:9]([CH:13]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:14]([O:16]CC)=[O:15])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[N:25]1[NH:26][N:27]=[N:28][C:29]=1[C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32](O)=[O:33].C1(N=C=NC2CCCCC2)CCCCC1.OC1C2N=NNC=2C=CC=1>C(O)C.CN(C=O)C.[Pd]>[N:28]1[NH:27][N:26]=[N:25][C:29]=1[C:30]1[CH:38]=[CH:37][CH:36]=[CH:35][C:31]=1[C:32]([NH:1][C:4]1[C:12]2[N:11]=[CH:10][N:9]([CH:13]([CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:14]([OH:16])=[O:15])[C:8]=2[CH:7]=[CH:6][CH:5]=1)=[O:33]

Participants

8

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 5551922-(1H-1,2,3,4-tetrazol-5-yl)benzoic acidHCID 21468887Ethyl 2-(4-nitro-1H-benzimidazol-1-yl)octanoateHCID 178418300HCID 178418300, compound

Product 1

HCID 214689902-[4-[2-(2H-tetrazol-5-yl)benzamido]-1H-benzimidazol-1-yl]octanoic acidYield 9.6%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 2-(4-nitro-1H-benzimidazol-1-yl)octanoate (4.44 mmoles, 1.48 g.) was hydrogenated over 0.6 g of 5% Pd/C in 100 ml ethanol. The catalyst was filtered over celite. The solution was concentrated. The residue was dissolved in 25 ml DMF and added to a stirred mixture of 2-(2H-tetrazol-5-yl)benzoic acid (4.21 mmoles, 0.80 g), dicyclohexylcarbodiimide (4.31 mmoles, 0.89 g.), and hydroxybenzotriazole (4.44 mmoles, 0.60 g) in 50 ml DMF. The reaction was stirred for 4 hours. The solid was removed by filtration. The reaction was concentrated. The residue was dissolved in ethyl acetate, and washed with water. The pH was adjusted to 8.0 using 5N NaOH. The aqueous layer was acidified to pH 2.5 using 2N HCL, and then extracted with ethyl acetate. The organic phase was separated, washed with water, dried and concentrated. The product was purified over silica gel eluted with 2% EtOH in ethyl acetate with 1% acetic acid to yield 0.18 g of 2-[4-[2-(2H-tetrazol-5-yl)benzamido]-1H-benzimidazol-1-yl]octanoic acid. (MS)

Workup

  1. filtrationThe catalyst was filtered over celite
  2. concentrationThe solution was concentrated
  3. dissolutionThe residue was dissolved in 25 ml DMF
  4. customThe solid was removed by filtration
  5. concentrationThe reaction was concentrated
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. washwashed with water
  8. extractionextracted with ethyl acetate
  9. customThe organic phase was separated
  10. washwashed with water
  11. customdried
  12. concentrationconcentrated
  13. customThe product was purified over silica gel
  14. washeluted with 2% EtOH in ethyl acetate with 1% acetic acid

Sources & evidence

ORD record
ord-164421251f2e46e1ab01007e22c7d6b5
Source dataset
uspto-grants-1997_12
Patent number
US05693633

Reaction notes

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