Reaction #7846

Reaction equation

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

Solvents

THF

Conditions

Workup

1. 1
   TemperatureThe mixture was heated
2. 2
   Temperatureat reflux for 1 h
3. 3
   FiltrationThe resultant organozinc reagent was filtered through a plug of Celite
4. 4
   Othertransferred to a flask
5. 5
   OtherThe mixture was degassed with bubbling argon for 15 min
6. 6
   Temperatureheated
7. 7
   Temperatureat reflux for 12 h
8. 8
   workup.ADDITIONThe reaction was poured into H2O (40 mL)
9. 9
   Extractionextracted with CH2Cl2 (2×30 mL)
10. 10
    DryingThe organic extracts were dried (MgSO4)
11. 11
    Concentrationconcentrated
12. 12
    Otherto afford a colorless solid
13. 13
    OtherPurification of the solid by flash chromatography on silica gel (EtOAc:hexanes 3:1)

Procedure

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)+.

Source