Reacción #9066

Ecuación de reacción

oxazole

n-butyllithium

methyl-4-bromobenzoate

n-butyllithium

→

methyl-4-(oxazol-2-yl)-benzoate

Rendimiento 42.0%

Disolventes

THF

—

hexanes

THF

ethyl acetate

—

hexanes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato slowly warm to 0° C.
2. 2
   workup.STIRRINGwas stirred for 45 min
3. 3
   TemperaturaThe resultant dark brown mixture was warmed
4. 4
   Temperaturato reflux
5. 5
   workup.STIRRINGstirred for 1 h
6. 6
   TemperaturaAfter cooling
7. 7
   Lavadowashed with water (1×20 mL) and brine (1×20 mL)
8. 8
   SecadoThe organic layer was dried (Na2SO4)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated
11. 11
    Otropurified by chromatography on silica gel (98:2 CH2C2/MeOH)

Procedimiento

To a solution of oxazole (0.285 mL, 4 mmol) in THF (40 mL) at −78° C. was added n-butyllithium (1.83 mL of a 2.4M solution in hexanes, 4.4 mmol) and the reaction stirred for 30 min at −78° C. then zinc chloride (12 mL of 1M solution in THF, 12 mmol) was added. The mixture was then allowed to slowly warm to 0° C. and was stirred for 45 min. A solution of methyl-4-bromobenzoate (0.860 g, 4 mmol) in THF (10 mL) was added followed by a solution of bis-(triphenylphosphine)-palladium (II) chloride (140 mg, 0.2 mmol) and n-butyllithium (0.17 mL of a 2.4M solution in hexanes, 0.4 mmol) in THF (4 mL). The resultant dark brown mixture was warmed to reflux and stirred for 1 h. After cooling, the reaction mixture was diluted with ethyl acetate (30 mL), then washed with water (1×20 mL) and brine (1×20 mL). The organic layer was dried (Na2SO4), filtered, concentrated and purified by chromatography on silica gel (98:2 CH2C2/MeOH) to give the desired methyl-4-(oxazol-2-yl)-benzoate (340 mg, 42%) as a yellow oil. 1H NMR (CDCl3) δ 3.94 (s, 3H), 7.28 (s, 1H), 7.76 (m, 1H), 8.09 (m, 4H).

Fuente