Reaction #3169

Reaction equation

3-bromothiophene

magnesium

product #25411-8

magnesium

1-bromo-3,4,5-trifluorobenzene

→

3(3,4,5-trifluorophenyl)thiophene

Conditions

Workup

1. 1
   Otherdried in an argon atmosphere for 3 to 4 minutes
2. 2
   TemperatureUpon cooling under the argon atmosphere, 50 ml of freshly dried tetrahydrofuran (product #T 397-4, manufactured by Fisher Scientific)
3. 3
   workup.DISTILLATIONwas previously distilled from a sodium/bentophenone mixture
4. 4
   workup.ADDITIONInto this mixture of magnesium and tetrahydrofuran
5. 5
   Temperaturethe flask was cooled (e.g., via an ice bath)
6. 6
   workup.STIRRINGcontinuously stirred for 2 hours
7. 7
   Otherto form a magnesium complex
8. 8
   workup.ADDITIONwas added to the magnesium complex at room temperature
9. 9
   workup.STIRRINGAfter stirring for 30 minutes
10. 10
    OtherThis coupling reaction mixture
11. 11
    Temperaturewas then heated (e.g., via an oil bath) for 0.5 hour
12. 12
    workup.STIRRINGwith continuous stirring at 60° C.

Procedure

In a first three-necked round-bottom flask (100 ml), metallic magnesium (52 mmol) (product #25411-8, manufactured by Aldrich Chemical) was flame dried in an argon atmosphere for 3 to 4 minutes. Upon cooling under the argon atmosphere, 50 ml of freshly dried tetrahydrofuran (product #T 397-4, manufactured by Fisher Scientific) was previously distilled from a sodium/bentophenone mixture and directly drawn into the flask from the distillation head. Into this mixture of magnesium and tetrahydrofuran was added 1-bromo-3,4,5-trifluorobenzene (26 mmol) (product #33084-1, manufactured by Aldrich Chemical), which remained in an argon atmosphere and was stirred. After the mixture was warmed to about 40° C. (after about 3 to 4 minutes), the flask was cooled (e.g., via an ice bath) and continuously stirred for 2 hours to form a magnesium complex. Anhydrous zinc chloride (ZnCl2) (31 mmol) (product #20808-6, manufactured by Aldrich Chemical) previously dried at 160° C. and weighed under vacuum conditions was added to the magnesium complex at room temperature. After stirring for 30 minutes, the zinc complex suspension was transferred (e.g., via Teflon tubing) under argon pressure to a second three-necked round-bottomed flask (250 mL) containing a solution of 3-bromothiophene (21 mmol) (product #10622-4, manufactured by Aldrich Chemical) and Pd(dppf)Cl2 catalyst (product #37967-0, manufactured by Aldrich Chemical). This coupling reaction mixture was then heated (e.g., via an oil bath) for 0.5 hour with continuous stirring at 60° C.

Source