Reacción #620465

Ecuación de reacción

magnesium chloride

potassium ethyl malonate

1-(3-(naphthalen-1-yloxy)propyl)-4-o-tolyl-1H-indole-2-carboxylic acid

1,1′-carbonyldiimidazole

→

title compound

ethyl 3-(1-(3-(naphthalen-1-yloxy)propyl)-4-o-tolyl-1H-indol-2-yl)-3-oxopropanoate

Disolventes

acetonitrile

triethylamine

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otroovernight
2. 2
   Temperaturathen cooled in an ice bath
3. 3
   workup.ADDITIONThe above-prepared solution was added dropwise to the first solution
4. 4
   OtroAfter this time the solvent was removed in vacuo
5. 5
   Temperaturacooled (ice bath), and aqueousHCl (12%)
6. 6
   workup.ADDITIONwas slowly added
7. 7
   TemperaturaThe mixture was warmed to room temperature
8. 8
   Extracciónextracted twice with ethyl acetate
9. 9
   LavadoThe combined layers were washed with aqueous NaHCO3, and brine
10. 10
    Secadodried over Na2SO4
11. 11
    Lavadoeluted with 5% ethyl acetate in hexane

Procedimiento

A solution of 1-(3-(naphthalen-1-yloxy)propyl)-4-o-tolyl-1H-indole-2-carboxylic acid (EXAMPLE 103) (536 mg) and 1,1′-carbonyldiimidazole (200 mg) in tetrahydrofuran (10 ml) was stirred at room temperature. overnight. To a suspension of potassium ethyl malonate (419 mg) in acetonitrile (10 ml) and triethylamine (0.515 ml) was added magnesium chloride (300 mg) and the mixture was stirred at room temperature for 4 hours then cooled in an ice bath. The above-prepared solution was added dropwise to the first solution, and the resultant suspension was stirred at room temperature for three days. After this time the solvent was removed in vacuo, the residue was taken up in toluene (50 ml), cooled (ice bath), and aqueousHCl (12%) was slowly added. The mixture was warmed to room temperature and extracted twice with ethyl acetate. The combined layers were washed with aqueous NaHCO3, and brine and dried over Na2SO4. After concentration of the solvent, the residue was loaded on a column and eluted with 5% ethyl acetate in hexane to give the title compound.

Fuente