Hydrochloric Acid → N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-nitroethyl]-2-(trifluoromethyl)benzamide

HRID 56051Notes

Reaction equation

HRID 56051 reaction equation
CC(C)([O-])C.[K+].[Cl:7][C:8]1[C:9]([CH2:18][N+:19]([O-:21])=[O:20])=[N:10][CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1.Cl[CH2:23][NH:24][C:25](=[O:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:32]([F:35])([F:34])[F:33].Cl>CN(C)C=O>[Cl:7][C:8]1[C:9]([CH:18]([N+:19]([O-:21])=[O:20])[CH2:23][NH:24][C:25](=[O:36])[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[C:32]([F:33])([F:35])[F:34])=[N:10][CH:11]=[C:12]([C:14]([F:17])([F:15])[F:16])[CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 573712083-Chloro-2-(nitromethyl)-5-(trifluoromethyl)pyridineHCID 118071537N-chloromethyl-2-(trifluoromethyl)benzamide

Product 1

HCID 118071604N-[2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]-2-nitroethyl]-2-(trifluoromethyl)benzamideYield 56.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 10.26 g of potassium tert-butoxide in 80 ml of N,N-dimethylformamide, 20.00 g of 3-chloro-2-nitromethyl-5-(trifluoromethyl)pyridine was added dropwise with stirring under cooling with ice, and after the addition, the mixture was stirred at the same temperature for another 30 minutes. Then, to the reaction mixture, 18.77 g of the N-chloromethyl-2-(trifluoromethyl)benzamide prepared in Step 2 in Synthetic Example 19 in 20 ml of N,N-dimethylformamide was added dropwise with stirring under cooling with ice, and after the addition, the mixture was stirred at room temperature for another 3 hours. After completion of the reaction, the reaction mixture was carefully poured into 150 ml of 5% aqueous hydrochloric acid under cooling with ice and extracted with ethyl acetate (100 ml×2). The resulting organic layers were combined, washed with water (100 ml×2) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The precipitated solid was purified with 30 ml of diisopropyl ether to obtain 19.80 g of the desired product as white crystals.

Workup

  1. temperatureunder cooling with ice
  2. additionafter the addition
  3. stirringthe mixture was stirred at the same temperature for another 30 minutes
  4. stirringwith stirring
  5. temperatureunder cooling with ice
  6. additionafter the addition
  7. stirringthe mixture was stirred at room temperature for another 3 hours
  8. customAfter completion of the reaction
  9. temperatureunder cooling with ice
  10. extractionextracted with ethyl acetate (100 ml×2)
  11. washwashed with water (100 ml×2)
  12. dry with materialdried over saturated aqueous sodium chloride
  13. customanhydrous sodium sulfate, and the solvent was evaporated under reduced pressure
  14. customThe precipitated solid was purified with 30 ml of diisopropyl ether

Sources & evidence

ORD record
ord-954218d5a3374291bc911075e5f234b8
Source dataset
uspto-grants-2016_09
Patent number
US09434684B2

Reaction notes

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