Propyl chloroformate → HCID 70026627, compound

HRID 1168409Notes

Reaction equation

HRID 1168409 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]([O:32][CH2:33][CH2:34][CH3:35])=[O:31]>CN(C)C=O>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9](=[C:18]([O:19][C:30]([O:32][CH2:33][CH2:34][CH3:35])=[O:31])[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 4

HCID 7998Propyl chloroformateHCID 24758Sodium hydrideHCID 675612-(Trifluoromethyl)benzoyl chlorideHCID 76784(4-tert-Butylphenyl)acetonitrile

Product 1

HCID 70026627HCID 70026627, compoundYield 69.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
45 °C

Procedure

A mixture comprising 2.0 g of 4-tert-butylbenzyl cyanide, 2.35 g of 2-trifluoromethylbenzoyl chloride and 8 ml of dimethylformamide, was dropwise added to a mixture comprising 0.84 g of 68% sodium hydride and 13 ml of dimethylformamide while maintaining the temperature at a level of from 40 to 50° C. After completion of the dropwise addition, the reaction was carried out for 30 minutes at room temperature. The reaction mixture was cooled with ice, and a mixture comprising 1.5 g of n-propyl chloroformate 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 and then washed 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 3.4 g of the desired product (isomer ratio 7:93) having a melting point of 44 to 45° C. The HPLC conditions for the analysis of this product were the same as in Preparation Example 1. Further, 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. washwashed 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-c111c1c2c91347a987b4e65564d01e3c
Source dataset
uspto-grants-2003_09
Patent number
US06624179B1

Reaction notes

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