Dimethylformamide → HCID 72826243, compound

HRID 1168408Notes

Reaction equation

HRID 1168408 reaction equation
[C:1]([C:5]1[CH:13]=[CH:12][C:8]([CH2:9][C:10]#[N:11])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[F:14][C:15]([F:26])([F:25])[C:16]1[CH:24]=[CH:23][CH:22]=[CH:21][C:17]=1[C:18](Cl)=[O:19].[H-].[Na+].Cl[C:30]1C=[CH:33][S:32][C:31]=1C(OCC)=O.CN(C)C=[O:43]>>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9](=[C:18]([O:19][C:33]([S:32][CH2:31][CH3:30])=[O:43])[C:17]2[CH:21]=[CH:22][CH:23]=[CH:24][C:16]=2[C:15]([F:26])([F:25])[F:14])[C:10]#[N:11])=[CH:12][CH:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 5

HCID 6228Dimethylformamide3×HCID 24758Sodium hydrideHCID 675612-(Trifluoromethyl)benzoyl chlorideHCID 76784(4-tert-Butylphenyl)acetonitrileHCID 12993676Ethyl 3-chlorothiophene-2-carboxylate

Product 1

HCID 72826243HCID 72826243, compound

Conditions

Temperature
40 °C

Procedure

A mixture comprising 2.0 g of 4-tert-butylbenzyl cyanide, 2.34 g of 2-trifluoromethylbenzoyl chloride and 8 ml of dimethylformamide, was dropwise added to a mixture comprising 0.83 g of 68% sodium hydride and 13 ml of dimethylformamide, while maintaining the temperature at 40° C. After completion of the dropwise addition, the reaction was carried out at room temperature for 30 minutes. The reaction mixture was cooled with ice, and a mixture comprising 1.77 g of ethyl chlorothiolformate and 1.2 ml of dimethylformamide, was dropwise added. After completion of the dropwise addition, the reaction was carried out for 30 minutes under cooling with ice. The reaction mixture was poured into ice water and extracted with methylene chloride, followed by washing with water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate/n-hexane=1/9) to obtain 3.9 g of a desired product (isomer ratio 2:98) having a melting point of 116 to 117° C. The HPLC conditions for the analysis of this product and the NMR spectrum data of this product are as follows.

Workup

  1. additionAfter completion of the dropwise addition
  2. temperatureThe reaction mixture was cooled with ice
  3. additionAfter completion of the dropwise addition
  4. waitthe reaction was carried out for 30 minutes
  5. temperatureunder cooling with ice
  6. extractionextracted with methylene chloride
  7. washby washing with water
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate/n-hexane=1/9)

Sources & evidence

ORD record
ord-750d326ac40e4e1797ea6dc0b13233ee
Source dataset
uspto-grants-2003_09
Patent number
US06624179B1

Reaction notes

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