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

HRID 56047Notes

Reaction equation

HRID 56047 reaction equation
CC(C)([O-])C.[K+].[Br:7][C:8]1[CH:9]=[C:10]([Cl:18])[C:11]([CH2:14][N+:15]([O-:17])=[O:16])=[N:12][CH:13]=1.Cl[CH2:20][NH:21][C:22](=[O:33])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]([F:32])([F:31])[F:30].Cl>CN(C)C=O>[Br:7][C:8]1[CH:9]=[C:10]([Cl:18])[C:11]([CH:14]([N+:15]([O-:17])=[O:16])[CH2:20][NH:21][C:22](=[O:33])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]([F:30])([F:32])[F:31])=[N:12][CH:13]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 23665647Potassium tert-butoxideHCID 118071537N-chloromethyl-2-(trifluoromethyl)benzamideHCID 1180717005-Bromo-3-chloro-2-(nitromethyl)pyridine

Product 1

HCID 118071621N-[2-(5-bromo-3-chloropyridin-2-yl)-2-nitroethyl]-2-(trifluoromethyl)benzamideYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To 4.2 g of potassium tert-butoxide in 72 ml of N,N-dimethylformamide, 7.8 g of 5-bromo-3-chloro-2-(nitromethyl)pyridine was added dropwise with stirring under cooling with ice, and after the addition, the mixture was stirred at the same temperature for another 1 hour. Then, to the reaction mixture, 4.7 g of the N-chloromethyl-2-(trifluoromethyl)benzamide prepared in Step 2 in Synthetic Example 19 in 30 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 2 hours. After completion of the reaction, the reaction mixture was carefully poured into 100 ml of ice-water, acidified with 10% aqueous hydrochloric acid 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 distilled off under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 6.0 g of the desired product as a pale yellow oil.

Workup

  1. temperatureunder cooling with ice
  2. additionafter the addition
  3. stirringthe mixture was stirred at the same temperature for another 1 hour
  4. stirringwith stirring
  5. temperatureunder cooling with ice
  6. additionafter the addition
  7. stirringthe mixture was stirred at room temperature for another 2 hours
  8. customAfter completion of the reaction
  9. extractionextracted with ethyl acetate (100 ml×2)
  10. washwashed with water (100 ml×2)
  11. dry with materialdried over saturated aqueous sodium chloride
  12. distillationanhydrous sodium sulfate, and the solvent was distilled off under reduced pressure
  13. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-2e244cda41b247ea9b1fe934cbfd7839
Source dataset
uspto-grants-2016_09
Patent number
US09434684B2

Reaction notes

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