Process for the enantiomeric resolution of apremilast intermediates
A process for the resolution of racemic 2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine using novel chiral salts is disclosed. An L-phenylalanine p-toluene-sulfonamide salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine and a di-p-toluoyl-L-tartaric acid salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine are also provided.
1. A process for the preparation of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine, comprising the steps of:
a. dissolving a racemic mixture of 2-(3-ethoxy-4-methoxyphenyl)-1-(methyl sulphonyl)-eth-2-ylamine in an organic solvent to form a solution;
b. adding L-phenylalanine p-toluene sulfonamide to the solution; and
c. isolating a L-phenylalanine p-toluene sulfonamide salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine,
wherein the chiral salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine is further converted into apremilast.
2. The process according to claim 1 , wherein the organic solvent is an alcoholic solvent.
3. The process according to claim 2 , wherein the alcoholic solvent is methanol.
4. A L-phenylalanine p-toluene-sulfonamide salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine.