Nitrogen → 4'-Fluoro-2-(4-trifluoromethylphenyl)acetophenone

HRID 968079

Reaction equation

HRID 968079 reaction equation
N#N.[H-].[Na+].[F:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12](N(C)C)[C:13]#N)=[CH:8][CH:7]=1.[F:18][C:19]([F:29])([F:28])[C:20]1[CH:27]=[CH:26][C:23](CCl)=[CH:22][CH:21]=1.S(=O)(=O)(O)[OH:31]>O.CN(C)C=O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:12](=[O:31])[CH2:13][C:23]2[CH:26]=[CH:27][C:20]([C:19]([F:29])([F:28])[F:18])=[CH:21][CH:22]=2)=[CH:8][CH:7]=1

Participants

8

Reactant 5

HCID 947Nitrogen3×HCID 1118Sulfuric AcidHCID 24758Sodium hydrideHCID 123096p-Trifluoromethylbenzyl chlorideHCID 113098562-(4-fluorophenyl)-2-(N,N-dimethylamino)acetonitrile

Product 1

HCID 98172164'-Fluoro-2-(4-trifluoromethylphenyl)acetophenoneYield 96.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent2×

Procedure

Into a 2 l four-necked flask equipped with a thermometer, a stirrer, a dropping funnel and a N2 gas supply tube, a N2 gas was supplied so that the interior of the flask became a N2 atmosphere. 400 ml of dimethylformamide and 35.0 g (0.9 mol) of sodium hydride (62% oil suspension) were charged, and a mixed solution comprising 133.5 g (0.75 mol) of 2-(4-fluorophenyl)-2-(N,N-dimethylamino)acetonitrile, 145.9 g (0.75 mol) of 4-(trifluoromethyl)benzyl chloride and 280 ml of dimethylformamide, was dropwise added over a period of one hour at from 10 to 25° C. under cooling with water and then further reacted at from 20 to 30° C. for one hour. Then, 330 g of 40% sulfuric acid aqueous solution was added to this reaction mixture and reacted at from 80 to 90° C. for one hour. After completion of the reaction, the reaction product was added to 2 e of water, and precipitated crystals were collected by filtration under reduced pressure and washed with water. Then, the crystals were washed and purified at 20° C. by means of 500 ml of isopropyl alcohol and then dried with hot air to obtain 204.7 g (yield: 95.2%) of the desired compound having a purity of 98.4% (by HPLC analysis).

Workup

  1. customInto a 2 l four-necked flask equipped with a thermometer, a stirrer, a dropping funnel
  2. customfurther reacted at from 20 to 30° C. for one hour
  3. customreacted at from 80 to 90° C. for one hour
  4. customAfter completion of the reaction
  5. customprecipitated crystals
  6. filtrationwere collected by filtration under reduced pressure
  7. washwashed with water
  8. washThen, the crystals were washed
  9. custompurified at 20° C. by means of 500 ml of isopropyl alcohol
  10. customdried with hot air

Sources & evidence

ORD record
ord-cb4320c710004ce9a6e39f87f79a12a0
Source dataset
uspto-grants-2005_10
Patent number
US06956132B2

Linked notes

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