Benzaldehyde → HCID 67273817, compound

HRID 598215Notes

Reaction equation

HRID 598215 reaction equation
[NH2:1][C:2]1[CH:10]=[N:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[OH-].[Na+].[CH:18](=O)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C([BH3-])#N.[Na+].[CH2:30](O)[CH3:31]>C(O)(=O)C>[C:19]1([CH2:18][NH:1][C:2]2[CH:10]=[N:9][CH:8]=[CH:7][C:3]=2[C:4]([O:6][CH2:30][CH3:31])=[O:5])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 6

HCID 240BenzaldehydeHCID 702EthanolHCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 4595313-Aminoisonicotinic acidHCID 5003444Sodium cyanoborohydride

Product 1

HCID 67273817HCID 67273817, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a suspension of 3-aminoisonicotinic acid (0.600 g, 4.35 mmol) in ethanol (20 mL) was added concentrated sulfuric acid (0.40 mL) at ambient temperature. The solution was then refluxed overnight, cooled to ambient temperature, and neutralized to pH ˜7 using 6N aqueous sodium hydroxide. The mixture was extracted with (3×20 mL) ethyl acetate. The combined organic portions were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was dissolved in methanol (20 mL) and treated with benzaldehyde (0.440 mL, 4.35 mmol). The solution was stirred at ambient temperature for 1 h and then treated with portionwise addition of sodium cyanoborohydride (0.920 g, 4.35 mmol) followed by acetic acid (0.20 mL). The resulting mixture was stirred at ambient temperature for 1 h and then concentrated in vacuo. The residue was treated with 5% aqueous sodium hydrogen carbonate and extracted with ethyl acetate (3×20 mL). The combined organic portions were dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was purified via flash column chromatography (10% methanol in dichloromethane) to afford the desired product as a yellow oil (0.500 g, 45%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.08 (s, 1H), 7.84 (d, J=5.3 Hz, 1H), 7.69 (d, J=4.5 Hz, 1H), 7.29-7.34 (m, 5H), 4.48 (d, J=5.6 Hz, 2H), 4.14 (q, J=7.2 Hz, 2H), 1.28 (t, J=7.2 Hz, 3H). MS(ES+) m/e 257 [M+H]+.

Workup

  1. temperatureThe solution was then refluxed overnight
  2. extractionThe mixture was extracted with (3×20 mL) ethyl acetate
  3. dry with materialThe combined organic portions were dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in methanol (20 mL)
  7. stirringThe resulting mixture was stirred at ambient temperature for 1 h
  8. concentrationconcentrated in vacuo
  9. additionThe residue was treated with 5% aqueous sodium hydrogen carbonate
  10. extractionextracted with ethyl acetate (3×20 mL)
  11. dry with materialThe combined organic portions were dried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified via flash column chromatography (10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-4c685a85bc054a969ae82f8d8f43cea4
Source dataset
uspto-grants-2011_03
Patent number
US07897612B2

Reaction notes

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