Reaction #2329067

Reaction equation

water

2-bromo-1,3-dichloro-5-methoxybenzene

5-(trifluoromethyl)-2-pyridylpiperazine

sodium tert-butoxide

→

1,3-dichloro-5-methoxy-2-{4-[5-(trifluoromethyl)(2-pyridyl)]piperazinyl}benzene

Solvents

toluene

Conditions

Workup

1. 1
   Temperaturewas maintained during a 24-hour period
2. 2
   TemperatureAfter this time the reaction mixture was cooled
3. 3
   OtherThe organic layer was separated
4. 4
   Extractionthe aqueous layer was extracted with two 75 mL portions of diethyl ether
5. 5
   Washwashed with 50 mL of an aqueous solution saturated with sodium chloride
6. 6
   DryingThe organic layer-extract combination was dried with sodium sulfate
7. 7
   Filtrationfiltered
8. 8
   Concentrationthe filtrate was concentrated under reduced pressure to a residue
9. 9
   workup.ADDITIONa mixture of products
10. 10
    Otherwas separated into its components by column chromatography on silica gel using 25% methylene chloride in hexane
11. 11
    Concentrationconcentrated under reduced pressure

Procedure

A stirred mixture of 3.0 grams (0.012 mole) of 2-bromo-1,3-dichloro-5-methoxybenzene (Step A), 2.7 grams (0.012 mole) of [5-(trifluoromethyl)-2-pyridylpiperazine (Step B), 0.02 gram (0.00024 mole) of tris(ydroxide eneacetone)dipalladium (0), 0.45 gram (0.00072 mole) of ydroxi-2,2′bis(diphenylphosphino)-1,1′-binaphthyl and 2.1 grains (0.022 mole) of sodium tert-butoxide in 150 mL of toluene was warmed to 80° C. where it was maintained during a 24-hour period. After this time the reaction mixture was cooled and poured into 250 mL of water. The organic layer was separated, and the aqueous layer was extracted with two 75 mL portions of diethyl ether. The organic layer and the extracts were combined and washed with 50 mL of an aqueous solution saturated with sodium chloride. The organic layer-extract combination was dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue, which was a mixture of products, was separated into its components by column chromatography on silica gel using 25% methylene chloride in hexane, then 50% methylene chloride in hexane as eluants. Appropriate fractions were combined and concentrated under reduced pressure, yielding 1.8 grams of 1,3-dichloro-5-methoxy-2-{4-[5-(trifluoromethyl)(2-pyridyl)]piperazinyl}benzene, and other appropriate fractions were combined and concentrated under reduced pressure, yielding 0.45 gram of 2-bromo-3-chloro-5-methoxy-1-{4-[5-(trifluoromethyl)(2-pyridyl)]piperazinyl}benzene. The NMR spectra of both compounds were consistent with the proposed structures.

Source