Reaction #595298

Reaction equation

2′,4′-difluoroacetophenone

diethyl 2-chlorobenzylphosphonate

sodium hydride

→

1-[1-(2-chlorophenyl)prop-1-en-2-yl]-2,4-difluorobenzene

Yield 26.0%

Solvents

DMF

water

DMF

Conditions

Workup

1. 1
   Washfreshly washed with dry heptane) in dry DMF (20 ml)
2. 2
   workup.STIRRINGThe resulting mixture was stirred at RT for 68 h
3. 3
   Extractionextracted with diethyl ether
4. 4
   OtherThe organic phase was dried
5. 5
   Concentrationconcentrated to dryness under reduced pressure
6. 6
   Otherthe residue was purified by chromatography on silica gel, which

Procedure

At 3° C., a solution of diethyl 2-chlorobenzylphosphonate (2.00 g, 7.61 mmol) in dry DMF (30 ml) was added to a stirred suspension of sodium hydride (60% by weight suspension in mineral oil, 365 mg, 9.13 mmol; freshly washed with dry heptane) in dry DMF (20 ml). After 1 h of stirring at 3° C., a solution of 2′,4′-difluoroacetophenone (1.31 g, 8.37 mmol) in dry DMF (20 ml) was added dropwise. The resulting mixture was stirred at RT for 68 h and then diluted with water and extracted with diethyl ether. The organic phase was dried and concentrated to dryness under reduced pressure, and the residue was purified by chromatography on silica gel, which gave 1-[1-(2-chlorophenyl)prop-1-en-2-yl]-2,4-difluorobenzene as a 93/7 mixture of diastereoisomers [colourless solid, 560 mg, yield 26%; GC/MS: m/z=264 (M+); HPLC/MS: log P(HCOOH)=5.05 (major diastereoisomer), 5.34 (minor diastereoisomer)].

Source