# US 10,370,329 B2 · Process for the enantiomeric resolution of apremilast intermediates

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- Number: US 10,370,329 B2
- Document ID: US10370329B2
- Status: Granted
- Kind: B2
- Application number: 15/573,290
- Filed: 2016-04-22
- Published: 2018-05-17
- Granted: 2019-08-06
- Earliest claimed: 2015-04-27
- Applicants: Mylan Laboratories Limited
- Inventors: Ramesh Dandala; Sureshbabu Jayachandra; Vipin Kumar Kaushik; Nageshwara Rao Achanta; Sivaprasad Dorasala
- Web page: https://patentgrep.com/patent/US10370329B2

## CPC

- C07D 209/48: with oxygen atoms in positions 1 and 3, e.g. phthalimide
- C07C 69/76: Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C 311/19: to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C 315/04: by reactions not involving the formation of sulfone or sulfoxide groups
- C07C 315/06: Separation; Purification; Stabilisation; Use of additives
- C07C 317/28: with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
- C07B 2200/07: Optical isomers
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07B: GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR (preparation of carboxylic acid esters by telomerisation C07C67/47; telomerisation C08F)

## Abstract

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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

The process according to claim 1, wherein the organic solvent is an alcoholic solvent.

### Claim 3 (depends on 2)

The process according to claim 2, wherein the alcoholic solvent is methanol.

### Claim 4

A L-phenylalanine p-toluene-sulfonamide salt of (S)-2-(3-ethoxy-4-methoxyphenyl)-1-(methylsulphonyl)-eth-2-ylamine.