Reacción #7846

Ecuación de reacción

2-[4-(bromomethyl)-3-methoxyphenyl]-1,3-benzoxazole

chlorotrimethylsilane

2-bromopyridine

1,2-dibromoethane

→

2-[3-methoxy-4-(pyridin-2-ylmethyl)phenyl]-1,3-benzoxazole

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe mixture was heated
2. 2
   Temperaturaat reflux for 1 h
3. 3
   FiltraciónThe resultant organozinc reagent was filtered through a plug of Celite
4. 4
   Otrotransferred to a flask
5. 5
   OtroThe mixture was degassed with bubbling argon for 15 min
6. 6
   Temperaturaheated
7. 7
   Temperaturaat reflux for 12 h
8. 8
   workup.ADDITIONThe reaction was poured into H2O (40 mL)
9. 9
   Extracciónextracted with CH2Cl2 (2×30 mL)
10. 10
    SecadoThe organic extracts were dried (MgSO4)
11. 11
    Concentraciónconcentrated
12. 12
    Otroto afford a colorless solid
13. 13
    OtroPurification of the solid by flash chromatography on silica gel (EtOAc:hexanes 3:1)

Procedimiento

A solution of 2-[4-(bromomethyl)-3-methoxyphenyl]-1,3-benzoxazole (320 mg, 1.0 mmol) and THF (10 mL) was treated with Zn powder (activated by grinding with mortar and pestle), a drop of chlorotrimethylsilane, and a drop of 1,2-dibromoethane. The mixture was heated at reflux for 1 h. The resultant organozinc reagent was filtered through a plug of Celite, and transferred to a flask containing 2-bromopyridine (360 mg, 2.0 mmol) and Pd(Ph3P)4 (115 mg, 0.1 mmol). The mixture was degassed with bubbling argon for 15 min, and heated at reflux for 12 h. The reaction was poured into H2O (40 mL) and extracted with CH2Cl2 (2×30 mL). The organic extracts were dried (MgSO4) and concentrated to afford a colorless solid. Purification of the solid by flash chromatography on silica gel (EtOAc:hexanes 3:1) afforded the desired 2-[3-methoxy-4-(pyridin-2-ylmethyl)phenyl]-1,3-benzoxazole as a yellow solid: 1H NMR (CDCl3, 300 MHz) δ 8.55 (d, 1H), 7.76–7.82 (m, 3H), 7.56–7.62 (d, 2H), 7.32–7.36 (m, 3H), 7.11–7.16 (m, 2H), 4.23 (s, 2H), 3.95 (s, 3H). MS (ESI) 317 (M+H)+.

Fuente