Reacción #9019

Ecuación de reacción

1,2-dibromoethane

tosyl cyanide

methyl-4(bromomethyl)benzoate

→

nitrile

Rendimiento 44.6%

4-bromomethyl-3-cyano-benzoic acid methyl ester

Rendimiento 44.6%

Disolventes

THF

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture was cooled to room temperature
2. 2
   TemperaturaThe mixture was cooled to 0° C.
3. 3
   workup.STIRRINGstirred for an additional 2 hours at 0° C
4. 4
   TemperaturaThe reaction mixture was cooled to −78° C.
5. 5
   ConcentraciónThe mixture was concentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (15 mL)
7. 7
   Filtraciónfiltered
8. 8
   OtroThe phases were separated
9. 9
   Extracciónthe aqueous layer was extracted with CH2Cl2 (3×50 mL)
10. 10
    SecadoThe combined organic extracts were dried (MgSO4)
11. 11
    Filtraciónfiltered
12. 12
    Concentraciónconcentrated under reduced pressure
13. 13
    OtroPurification by column chromatography on silica gel (Hexanes/EtOAc, 10:1)

Procedimiento

A suspension of zinc dust (792 mg, 12.12 mmol) and 1,2-dibromoethane (44 μL, 0.51 mmol) in THF (3 mL) was stirred at 70° C. for 10 minutes. The mixture was cooled to room temperature and chlorotrimethylsilane (45 μL, 0.36 mmol) was added. The mixture was cooled to 0° C. and a solution of methyl-4(bromomethyl)benzoate (2.314 g, 10.10 mmol) in THF (11 mL) was added at 0° C. over 2 hours and then stirred for an additional 2 hours at 0° C. The reaction mixture was cooled to −78° C. and a solution of tosyl cyanide (1.556 g, 8.59 mmol) in THF (11 mL) was added and the resultant mixture stirred at room temperature for 16 hours. The mixture was concentrated under reduced pressure, diluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (15 mL) and filtered. The phases were separated and the aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (Hexanes/EtOAc, 10:1) afforded the desired nitrile (973 mg) as a 16:1 mixture (desired product/side product).

Fuente