Reacción #42344

Ecuación de reacción

lithium hydroxide monohydrate

oxazole

n-butyllithium

methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate

→

title compound

3-{[Methyl(propyl)amino]carbonyl}-5-(1,3-oxazol-2-yl)benzoic acid

Disolventes

tetrahydrofuran methanol water

chloroform

ethyl acetate

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe reaction mixture is heated
2. 2
   Temperaturaat reflux for 2 h
3. 3
   TemperaturaThe reaction mixture is cooled
4. 4
   Lavadowashed with water, and brine
5. 5
   Secadodried (sodium sulfate)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated under reduced pressure
8. 8
   OtroPurification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)
9. 9
   Otroprovides a solid
10. 10
    workup.ADDITIONis added
11. 11
    Lavadowashed with 1N hydrochloric acid (aq), water, and brine
12. 12
    Secadodried (sodium sulfate)
13. 13
    Filtraciónfiltered
14. 14
    Concentraciónconcentrated under reduced pressure

Procedimiento

To a −70° C. stirred solution of oxazole (330 mg, 4.8 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 3.3 mL, 5.3 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 14.5 mL, 14.5 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-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate (1.6 g, 4.5 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (221 mg, 0.19 mmol). The reaction mixture is heated at reflux for 2 h. The reaction mixture is cooled, diluted with ethyl acetate, washed with water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides a solid. The solid is redissolved in 1:1:1 tetrahydrofuran/methanol/water (9 mL), and lithium hydroxide monohydrate (311 mg, 7.4 mmol) is added and stirred 2 h at room temperature. The reaction is diluted in chloroform and washed with 1N hydrochloric acid (aq), water, and brine, dried (sodium sulfate), filtered and concentrated under reduced pressure to give the title compound. ESI MS m/z 287.3 [M−H]−.

Fuente