Heptanal → HCID 66811753, compound

HRID 1097850Notes

Reaction equation

HRID 1097850 reaction equation
[CH3:1][O:2][C:3](=[O:21])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][CH2:13][CH2:14][NH:15][CH2:16][CH3:17])=[C:8]([N+:18]([O-])=O)[CH:7]=1.[CH:22](=O)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].O.O.Cl[Sn]Cl>CC(O)=O.CO>[CH3:1][O:2][C:3](=[O:21])[CH:4]=[CH:5][C:6]1[CH:11]=[CH:10][C:9]2[N:12]([CH2:13][CH2:14][NH:15][CH2:16][CH3:17])[C:22]([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])=[N:18][C:8]=2[CH:7]=1

Participants

6

Reactant 3

HCID 8130HeptanalHCID 61436Stannous chloride dihydrateHCID 66811763HCID 66811763, compound

Product 1

HCID 66811753HCID 66811753, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 3-[4-(2-ethylamino-ethylamino)-3-nitro-phenyl]-acrylic acid methyl ester (8.174 g, 27.87 mmol) and heptaldehyde (4.85 g, 42.47 mmol, 1.52 eq) in AcOH and MeOH (1:9 v/v, 300 mL) was added SnCl2.2H2O (31.45 g, 139.4 mmol, 5 eq) in portions. The resulting mixture was heated to 40° C. with stirring. The progress of the reaction was monitor by LC/MS. When the reaction was completed, solvent was removed under reduced pressure below 40° C. The resultant residue was diluted with EtOAc (50 mL) then basified (pH>10) with saturated aqueous Na2CO3 and extracted with dichloromethane (×3). Filtration may be needed to remove the white precipitates or suspension derived from Tin in order to get clearly separated layers. The organic extracts were combined, dried (Na2SO4), filtered, and evaporated to dryness. The resulting oily residue was purified by flash column chromatography (silica, φ67×65 mm, solvent MeOH/DCM gradient from 0 to 10%). 3-[1-(2-ethylamino-ethyl)-2-hexyl-1H-benzoimidazol-5-yl]-acrylic acid methyl ester was obtained as yellow solid (4.445 g, 44.6%). HPLC purity at 254 nm: 98.8%, tR=1.71 min. LCMS (ESI) m/z: 358 ([M+H]+). 1H NMR (CDCl3) δ 7.88 (1H, d, J=1.2 Hz), 7.83 (1H, d, J=16.0 Hz), 7.43 (1H, dd, J=8.4, 1.4 Hz), 7.33 (1H, d, J=8.4 Hz), 6.43 (1H, d, J=15.9 Hz), 4.22 (2H, t, J=6.6 Hz), 3.80 (3H, s), 3.01 (2H, t, J=6.6 Hz), 2.89 (2H, t, J=7.9 Hz), 2.65 (2H, q, J=7.1 Hz), 1.91 (2H, pentet, J=7.8 Hz), 1.46 (2H, m), 1.35 (4H, m), 1.07 (3H, t, J=7.1 Hz), 0.90 (3H, t, J=7.0 Hz). The solid could be recrystallized from Hexanes-ether to give a white or pale yellow solid with HPLC purity at 254 nm: 99.2%.

Workup

  1. customsolvent was removed under reduced pressure below 40° C
  2. additionThe resultant residue was diluted with EtOAc (50 mL)
  3. extractionextracted with dichloromethane (×3)
  4. filtrationFiltration
  5. customto remove the
  6. customwhite precipitates
  7. customto get clearly separated layers
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated to dryness
  11. customThe resulting oily residue was purified by flash column chromatography (silica, φ67×65 mm, solvent MeOH/DCM gradient from 0 to 10%)

Sources & evidence

ORD record
ord-32aa870e3d37450b9f525c786bb20141
Source dataset
uspto-grants-2012_03
Patent number
US08143282B2

Reaction notes

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