Reacción #8221

Ecuación de reacción

[2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

dimethylformamide

sodium hydride

methyl-2-chloroacetate

→

[2-(7-(methoxycarbomethoxy)-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester

Rendimiento 30.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONadded portion-wise over a 10 minute period
2. 2
   TemperaturaThe mixture is cooled in an ice/water bath
3. 3
   OtroThe ice bath is removed
4. 4
   OtroThe reaction is then quenched with saturated brine
5. 5
   Extracciónextracted with ethyl acetate
6. 6
   SecadoThe ethyl acetate layer is dried
7. 7
   Concentraciónconcentrated
8. 8
   Otroto give a crude residue, which
9. 9
   Otrois purified by silica gel chromatography (gradient elution, chloroform with 1%–10% of 20% methanol in acetonitrile)

Procedimiento

A solution of [2-(7-hydroxy-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (609 mg, 2.0 mmol) is dissolved in dry dimethylformamide (30 ml) under a nitrogen atmosphere and treated with sodium hydride (84 mg, 2.1 mmol, 60% dispersion in oil) added portion-wise over a 10 minute period. The mixture is cooled in an ice/water bath and methyl-2-chloroacetate (434 mg, 4.0 mmol) is added drop-wise over 20 minutes. The ice bath is removed and the mixture stirred at room temperature for 15 hours. The reaction is then quenched with saturated brine and extracted with ethyl acetate. The ethyl acetate layer is dried and concentrated to give a crude residue, which is purified by silica gel chromatography (gradient elution, chloroform with 1%–10% of 20% methanol in acetonitrile) to give 230 mg of [2-(7-(methoxycarbomethoxy)-1H-indol-3-yl)-1,1-dimethyl-ethyl]-carbamic acid tert-butyl ester (30%).

Fuente