Trimethylsilyl iodide → (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-hydroxy-isoindole-1,3-dione

Participants

Reaction Steps

3-Amino-4-methoxy-phthalic anhydride is prepared according to a procedure based on Rudolf Grewe (Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1938), 71B 907-11). A stirred mixture of 3-amino-4-methoxy-phthalic anhydride (1 mmol) and (S)-1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethylamine (1 mmol) in acetic acid is heated to reflux overnight. The solvent is removed in vacuo. The residue is extracted with water and ethyl acetate. The organic layer is dried over MgSO4. The solvent is removed in vacuo to give the crude (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dione. The product is purified by column chromatography or recrystallization. To a stirred solution of (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-methoxy-isoindole-1,3-dione (0.5 mmol) in anhydrous CH2Cl2, is added iodotrimethylsilane (3 mmol). The mixture is stirred at room temperature for 24 hours. The reaction mixture is diluted with brine and is extracted with CH2Cl2. The solvent is removed in vacuo to afford crude (S)-4-amino-2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-5-hydroxy-isoindole-1,3-dione. The product is purified by column chromatography or recrystallization.

Provenance & Evidence