Réaction #40497

Équation de réaction

H2O

Sodium bis(trimethylsilyl)amide

3-cyanomethyl-indole-1-carboxylic acid tert-butyl ester

Iodomethane

→

3-(cyano-methyl-methyl)-indole-1-carboxylic acid tert-butyl ester

Rendement 79.4%

Solvants

EtOAc

THF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGthe reaction mixture was stirred 1.5 hr
2. 2
   Autrewas brought to RT
3. 3
   AutreThe aqueous layer was removed
4. 4
   Extractionextracted with EtOAc (250 ml)
5. 5
   LavageThe combined organic layers were washed with aqueous HCl (1N, 3×50 ml)
6. 6
   Séchagedried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Concentrationconcentrated to an orange oil
9. 9
   AutrePurification via column chromatography (hexanes:ethyl acetate)

Mode opératoire

A stirred solution of 3-cyanomethyl-indole-1-carboxylic acid tert-butyl ester (2.15 g, 8.39 mmol) in THF (40 ml) was cooled to −78° C. under an argon atmosphere. Sodium bis(trimethylsilyl)amide (1 M in THF, 10 ml, 10 mmol) was added thereto and the cold solution was stirred for 30 minutes. Iodomethane (627 uL, 10 mmol) was added thereto and the reaction mixture was stirred 1.5 hr while gradually warming to 0° C. H2O (100 ml) was added thereto and the solution was brought to RT and diluted with EtOAc (250 ml). The aqueous layer was removed and extracted with EtOAc (250 ml). The combined organic layers were washed with aqueous HCl (1N, 3×50 ml), followed by brine, then dried over MgSO4, filtered, and concentrated to an orange oil. Purification via column chromatography (hexanes:ethyl acetate) gave 3-(cyano-methyl-methyl)-indole-1-carboxylic acid tert-butyl ester (1.8 g).

Source