Reaktion #589449

Reaktionsgleichung

(R)-1-cyclopropylethanol

2-(4-Amino-phenyl)-6-(2-chloro-ethoxy)-1-cyclobutyl-1H-indole-3-carbonitrile

toluene

phosgene

→

{4-[6-(2-Chloro-ethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester

Ausbeute 77.0%

Lösungsmittel

HCl

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeSolvent was removed
2. 2
   Sonstigethe white solid obtained
3. 3
   workup.STIRRINGSolution was stirred in a sealed tube for 16 h at room temperature
4. 4
   Extraktionextracted with EtOAc (2×100 mL)
5. 5
   Trocknendried over MgSO4
6. 6
   Einengenconcentrated
7. 7
   SonstigeSolid product was triturated with ether

Vorschrift

2-(4-Amino-phenyl)-6-(2-chloro-ethoxy)-1-cyclobutyl-1H-indole-3-carbonitrile (800 mg, 2.19 mmol) was dissolved in phosgene in toluene (2M, 10 mL, 5.00 mmol) and stirred for 2 h at 80° C. in a sealed tube. Solvent was removed and the white solid obtained was suspended in 1 ml of DCE. To this solution was added (R)-1-cyclopropylethanol (400 uL, 5.28 mmol) and DMAP (268 mg, 2.19 mmol). Solution was stirred in a sealed tube for 16 h at room temperature. An aqueous workup was performed in 0.5M HCl (200 mL) and extracted with EtOAc (2×100 mL). The organic layers were combined, dried over MgSO4 and concentrated. Solid product was triturated with ether to generate 800 mg (77% yield) of {4-[6-(2-Chloro-ethoxy)-3-cyano-1-cyclobutyl-1H-indol-2-yl]-phenyl}-carbamic acid 1-cyclopropyl-ethyl ester, as a white solid.

Quelle