Apremilast synthesis

Yield:-

Reaction Conditions:

with aluminum (III) chloride in dichloromethane at 20; for 1 h;

Steps:

5.2

5.2 (S)-N-{2-[1-(3-Hydroxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide To a stirred solution of (S)-N-{2-[1-(3-ethoxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide (0.55 mmol) in anhydrous CH₂Cl₂ at room temperature, is added Ala (1.10 mmol). After stirring for 1 hour, water is added. The product is extracted into CH₂Cl₂ and is dried over Na₂SO₄. The solvent is removed to give crude (S)-N-{2-[1-(3-hydroxy-4-methoxy-phenyl)-2-methanesulfonyl-ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}-acetamide. The product is purified by chromatography or recrystallization.

References:

US2012/178708,2012,A1 Location in patent:Page/Page column 18