(S)-CSA salt of S-ketamine, (R)-CSA salt of S-ketamine and processes for the preparation of S-ketamine
AssigneeJanssen Pharmaceutica NV
InventorsCheng Yi Chen, Oliver Floegel, Michael Justus, Adrian Maurer, Karl Reuter, Tobias Strittmatter, Tobias Wedel
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Abstract
The present invention is directed to processes for the preparation of esketamine. The present invention is further directed to processes for the resolution of S-ketamine from a racemic or enantiomerically enriched mixture of ketamine. The present invention is further directed to an (S)-CSA salt of S-ketamine, more particularly a monohydrate form of the (S)-CSA salt of S-ketamine; and to an (R)-CSA salt of R-ketamine.
Claims15
A process for the preparation of a monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine comprising
- reacting ketamine with (S)-camphorsulfonic acid, wherein the (S)-camphorsulfonic acid is present in an amount in the range of from about 0.5 to about 2.0 molar equivalents (relative to the molar amount of ketamine);
- in the presence of water, wherein the water is present in an amount in the range of from about 3.5% to about 15%;
- in an organic solvent selected from the group consisting of an ether, a ketone, and mixtures thereof;
- at a temperature in the range of from about 20° C. to about solvent reflux temperature;
- to yield the corresponding monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine;
- wherein the monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine is present in an enantiomeric excess in the range of from about 50% to about 100%.
A process for the preparation of a monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine comprising
- reacting racemic ketamine with (S)-camphorsulfonic acid, wherein the (S)-camphorsulfonic acid is present in an amount of about 1 molar equivalents (relative to the molar amount of ketamine);
- in the presence of water, wherein the water is present in an amount in the range of from about 6% to about 8%;
- in 2-methyl-THF;
- at a temperature of about 70° C.;
- to yield the corresponding monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine;
- wherein the monohydrate form of (S)-camphorsulfonic acid salt of S-ketamine is present in an enantiomeric excess in the range of from about 80% to about 100%.
Dependencies are inferred from the claim text.