Process for the preparation of pleuromutilins
A process for the preparation of 14-O-[(N-(3-methyl-2-amino-butyryl-piperidinyl)sulfanyl) acetyl]mutilins of formula (I) feasible for large-scale production of high purity products, and wherein the carbon atom at the piperidine ring attached to the sulphur atom is either in the (S)-configuration or in the (R)-configuration, and a new crystalline form of 14-O-[(N-3-methyl-2-(R)-amino-butyryl-piperidine-3(S)-yl)sulfanyl)acetyl]mutilin-hydrochloride.
1. Crystalline 14-O-[(N-3-methyl-2-(R)-amino-butyryl-piperidine-3(S)-yl)sulfanyl)acetyl]mutilin hydrochloride with XRD peaks 2-theta of
Angle (2-Theta)
6.2±0.2
10.9±0.2
12.3±0.2
13.4±0.2
14.1±0.2
20.8±0.2,
and having a 3-(S)-diastereomeric excess of ≧97%.
2. Process for preparation of crystalline compound of claim 1 , comprising the steps of
dissolving and warming 14-O-[(N-3-Methyl-2-(R)-amino-butyryl-piperidine-3(S)-yl)sulfanyl)acetyl]mutilin hydrochloride in an aqueous medium
optionally seeding the solution and stifling at elevated temperature
cooling the obtained suspension and stifling at ambient temperature
isolating crystalline product and optionally repeating the procedure.
3. Pharmaceutical compositions containing crystalline 14-O-[(N-3-methyl-2-(R)-amino-butyryl-piperidine-3(S)-yl)sulfanyl)acetyl]mutilin-hydrochloride with XRD peaks 2-theta of
Angle (2-Theta)
6.2±0.2
10.9±0.2
12.3±0.2
13.4±0.2
14.1±0.2
20.8 ±0.2
and having a 3-(S)-diastereomeric excess of ≧97%.