Reaction #1929011

Reaction equation

1-ethynyl-4-propylcyclohexane

1-bromo-4-ethoxy-2,3-difluorobenzene

→

1-ethoxy-2,3-difluoro-4-(4-propylcyclohexylethynyl)benzene

Solvents

triethylamine

MTBE

hydrochloric acid

Conditions

Workup

1. 1
   TemperatureAfter cooling
2. 2
   OtherThe organic phase is separated off
3. 3
   Extractionthe aqueous phase is extracted with MTBE
4. 4
   WashThe combined organic phases are washed with sodium chloride solution
5. 5
   Otherdried
6. 6
   ConcentrationThe solution is concentrated to dryness
7. 7
   Otherthe residue is purified by column chromatography (SiO2, n-heptane:chlorobutane=9:1)
8. 8
   OtherThe further purification
9. 9
   Otheris carried out by recrystallisation from n-heptane

Procedure

A mixture of 20.6 g (0.14 mol) of 1-ethynyl-4-propylcyclohexane, 25.0 g (0.11 mol) of 1-bromo-4-ethoxy-2,3-difluorobenzene, 2.22 g (3.16 mmol) of bis(triphenylphosphine)palladium(II) chloride and 603 mg (3.16 mmol) of copper(I) iodide in 440 ml of triethylamine is warmed at 50° C. for 19 h. After cooling, the mixture is diluted with MTBE and neutralised using dil. hydrochloric acid. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed with sodium chloride solution and dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, n-heptane:chlorobutane=9:1). The further purification is carried out by recrystallisation from n-heptane, giving 1-ethoxy-2,3-difluoro-4-(4-propylcyclohexylethynyl)benzene as a colourless solid (m.p. 64° C.). This has the phase sequence: C 64° C. I. The properties, extrapolated from a 10% solution in ZLI-4792, are:

Source