Formic Acid → 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbaldehyde

HRID 1796486Notes

Reaction equation

HRID 1796486 reaction equation
[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:14]#N)=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1.C(O)=[O:27]>[Ni]>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([CH:14]=[O:27])=[CH:13][C:8]=3[N:7]=[C:6]2[CH2:16][C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 284Formic AcidHCID 221813091-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbonitrile

Product 1

HCID 221812871-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbaldehydeYield 82%

Reagents, catalysts & solvents 1

HCID 935NickelCatalyst

Conditions

Temperature
90 °C

Procedure

To a solution of 1-(cyclopropylmethyl)-2-(4-ethoxybenzyl)-1H-benzimidazole-5-carbonitrile (0.049 g, 0.149 mmol) in 50% aqueous formic acid (1 mL) was added a catalytic amount of Raney nickel (50% suspension in water) and the resulting mixture was heated at 90° C. for 6 hours. The mixture was filtered through a short pad of diatomaceous earth and washed with EtOAc. The solvent was evaporated in vacuo and the residue was taken up into EtOAc (5 mL). The organic phase was washed with 1 N NaOH (2×2 mL) and brine (2 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by silica gel column chromatography (40% EtOAc/hexanes) to provide the title compound (0.041 g, 82%) as a white solid. 1H NMR (acetone-d6): δ 10.16 (s, 1H), 8.29 (s, 1H), 7.90 (d, J=8.4 Hz, 1H), 7.76 (d, J=8.4 Hz, 1H), 7.34 (d, J=8.4 Hz, 2H), 6.94 (d, J=8.4 Hz, 2H), 4.44 (s, 2H), 4.24 (d, J=6.4 Hz, 2H) 4.07 (q, J=6.8 Hz, 2H), 1.40 (t, J=7.0 Hz, 3H), 1.27–1.14 (m, 1H), 0.58–0.49 (m, 2H), 0.48–0.38 (m, 2H). MS (ESI) (M+H)+=335.

Workup

  1. filtrationThe mixture was filtered through a short pad of diatomaceous earth
  2. washwashed with EtOAc
  3. customThe solvent was evaporated in vacuo
  4. washThe organic phase was washed with 1 N NaOH (2×2 mL) and brine (2 mL)
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel column chromatography (40% EtOAc/hexanes)

Sources & evidence

ORD record
ord-6e8b00c322ea4867950844743ae1af09
Source dataset
uspto-grants-2006_04
Patent number
US07030139B2

Reaction notes

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