Reacción #42350

Ecuación de reacción

n-butyllithium

oxazole

methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate

→

title compound

Methyl 3-[(dipropylamino)carbonyl]-5-(1,3-oxazol-2-yl)benzoate

Disolventes

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowithout further purification
2. 2
   Otroin the following reaction
3. 3
   TemperaturaThe reaction mixture is heated
4. 4
   Temperaturaat reflux for 3 h
5. 5
   TemperaturaThe reaction mixture is cooled
6. 6
   Filtraciónfiltered
7. 7
   Lavadowashed with saturated sodium bicarbonate, water, and brine
8. 8
   Secadodried (sodium sulfate)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated under reduced pressure
11. 11
    OtroPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)

Procedimiento

3-[(Dipropylamino)carbonyl]-5-iodobenzoic acid (12 g, 32 mmol) is dissolved in 20% methanol/benzene (480 mL), and 2M trimethylsilyldiazomethane in hexane (19 mL, 38 mmol) is added slowly. Upon completion of the addition, the solution is concentrated under reduced pressure to give methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate for use without further purification in the following reaction. To a −70° C. stirred solution of oxazole (120 mg, 1.7 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 1.2 mL, 1.9 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 5.2 mL, 5.2 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate (643 mg, 1.6 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (80 mg, 0.07 mmol). The reaction mixture is heated at reflux for 3 h. The reaction mixture is cooled, diluted with ethyl acetate, filtered, washed with saturated sodium bicarbonate, water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides the title compound in pure form. 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.80 (s, 1H) 7.32 (s, 1H), 3.52 (t, 2H), 3.22 (t, 2H), 1.75 (m, 2H), 1.30 (m, 2H), 0.97 (t, 3H), 0.79 (t, 3H).

Fuente