Ethanol → N,N-Bis-(4-methoxybenzyl)-(6-ethoxy-5-trifluoromethylpyridine-2-yl)amine

HRID 545084Notes

Reaction equation

HRID 545084 reaction equation
[O-:1][CH2:2][CH3:3].[Na+].[Na].CCO.[CH3:9][O:10][C:11]1[CH:38]=[CH:37][C:14]([CH2:15][N:16]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[C:28](Cl)[N:27]=2)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1>C1COCC1>[CH3:9][O:10][C:11]1[CH:38]=[CH:37][C:14]([CH2:15][N:16]([C:26]2[CH:31]=[CH:30][C:29]([C:32]([F:35])([F:34])[F:33])=[C:28]([O:1][CH2:2][CH3:3])[N:27]=2)[CH2:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)=[CH:13][CH:12]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 2723922Sodium ethoxideHCID 5360545Sodium2×HCID 86605106N,N-Bis-(4-methoxybenzyl)-(6-chloro-5-trifluoromethylpyridine-2-yl)amine

Product 1

HCID 67190754N,N-Bis-(4-methoxybenzyl)-(6-ethoxy-5-trifluoromethylpyridine-2-yl)amine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add freshly prepared sodium ethoxide [made by adding sodium (1.26 g, 54.9 mmol) to 25 mL of absolute EtOH, and stirring until all the sodium is dissolved] dropwise to a solution of N,N-bis-(4-methoxybenzyl)-(6-chloro-5-trifluoromethyl-pyridine-2-yl)amine (8.0 g, 18.3 mmol) in 150 mL THF. Heat the reaction mixture to reflux for 45 hours. During reflux, the reaction mixture turns brown. After cooling to room temperature, remove the solvent under vacuum. Take up the residue in CH2Cl2 (150 mL) and wash with water (100 mL). Extract the aqueous layer once more with 100 mL CH2Cl2. Wash the combined CH2Cl2 extracts with brine (100 mL), dry (Na2SO4), filter, and evaporate to give a brown oil/solid mix. Purification by column chromatography affords the title product as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.51 (d, 1H, J=8.8 Hz), 7.13 (m, 4H), 6.86 (m, 4H), 6.0 (d, 1H, J=8.8 Hz), 4.67 (s, 4H), 4.37 (q, 2H, J=6.8 and 7.6 Hz), 3.80 (s, 6H), 1.32 (t, 3H, J=6.8 Hz). Mass spec. (447.34, M+H).

Workup

  1. temperatureHeat the reaction mixture
  2. temperatureto reflux for 45 hours
  3. temperatureDuring reflux
  4. customremove the solvent under vacuum
  5. washwash with water (100 mL)
  6. extractionExtract the aqueous layer once more with 100 mL CH2Cl2
  7. washWash the combined CH2Cl2
  8. dry with materialdry (Na2SO4)
  9. filtrationfilter
  10. customevaporate
  11. customto give a brown oil/solid
  12. additionmix
  13. customPurification by column chromatography

Sources & evidence

ORD record
ord-c12ae9acae3e40a9b460ce045e429e67
Source dataset
uspto-grants-2011_05
Patent number
US07935702B2

Reaction notes

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