Abstract: The present invention relates to an improved process for the preparation of substantially pure Mexiletine hydrochloride (1) with purity greater than 99.0 %.
We claim:
1. A process for the preparation of Mexiletine hydrochloride (1) having purity
greater than 99.0 % by HPLC comprising:
a) acylating 2,6-dimethylphenol (5) with chloroacetone in the presence of an aprotic solvent and a base to obtain l-(2,6-dimethylphenoxy) propan-2-one (4);
b) reacting l-(2,6-dimethylphenoxy)propan-2-one (4) with hydroxylamine hydrochloride in the presence of a protic solvent to obtain l-(2',6'-dimethylphenoxy)-2-propane oxime (3);
c) reducing l-(2',6'-dimethylphenoxy)-2-propane oxime with hydrogen gas in the presence of a metal reducing agent in alcohol to obtain l-(2',6'-dimethylphenoxy)-2-amino-propane (2) (Mexiletine base); and
d) treating Mexiletine base (2) with isopropyl alcoholic hydrochloric acid in an aprotic solvent to obtain Mexiletine hydrochloride (1).
2. The process according to claim 1, wherein the aprotic solvent used in step a) can be selected from tetrahydrofuran, dichloromethane, ethyl acetate, acetone, dichloromethane.
3. The process according to claim 1, wherein the base used in step a) can be selected from sodium hydride, triethylamine, N,N-diisopropylethyl amine, 4-dimethylamino pyridine, sodium carbonate, potassium carbonate.
4. The process according to claim 1, wherein the protic solvent used in step b) can be selected from methanol, ethanol, isopropanol, water.
5. The process according to claim 1, wherein the metal reducing agent used in step c) can be selected from palladium on carbon, Raney nickel, platinum.
6. The process according to claim 1, wherein the aprotic solvent used in step d) can be selected from tetrahydrofuran, dichloromethane, ethyl acetate, acetone, dichloromethane.
7. A process for the purification of Mexiletine hydrochloride (1), comprising:
f) providing a solution of Mexiletine hydrochloride (1) in a protic solvent;
g) stirring the reaction mixture and filtering;
h) distilling off the solvent under vacuum and adding an aprotic solvent; i) filtering the reaction mixture and washing with an aprotic solvent; and j) isolating pure Mexiletine hydrochloride (1).
8. The process according to claim 7, wherein the protic solvents used can be selected from methanol, ethanol, isopropanol, water and the aprotic solvents used can be selected from ethyl acetate, methyl tertiary butyl ether, acetone, dichloromethane.
9. The process according to claim 7, wherein the Mexiletine hydrochloride (1) is having purity greater than 99.0 % and one or more of the following:
a) less than 0.15 % of impurity A;
b) less than 0.15% of impurity C; and
c) less than 0.15% of impurity D.
| # | Name | Date |
|---|---|---|
| 1 | 201941025908-IntimationOfGrant17-02-2025.pdf | 2025-02-17 |
| 1 | 201941025908-PROVISIONAL SPECIFICATION [28-06-2019(online)].pdf | 2019-06-28 |
| 2 | 201941025908-FORM 1 [28-06-2019(online)].pdf | 2019-06-28 |
| 2 | 201941025908-PatentCertificate17-02-2025.pdf | 2025-02-17 |
| 3 | 201941025908-DRAWINGS [28-06-2019(online)].pdf | 2019-06-28 |
| 3 | 201941025908-ABSTRACT [12-02-2025(online)].pdf | 2025-02-12 |
| 4 | Form 1_After Filing_15-07-2019.pdf | 2019-07-15 |
| 4 | 201941025908-CLAIMS [12-02-2025(online)].pdf | 2025-02-12 |
| 5 | Correspondence by Applicant_Form 1_15-07-2019.pdf | 2019-07-15 |
| 5 | 201941025908-FER_SER_REPLY [12-02-2025(online)].pdf | 2025-02-12 |
| 6 | 201941025908-FORM 3 [27-06-2020(online)].pdf | 2020-06-27 |
| 6 | 201941025908-FER.pdf | 2024-08-12 |
| 7 | 201941025908-FORM 18 [08-06-2023(online)].pdf | 2023-06-08 |
| 7 | 201941025908-ENDORSEMENT BY INVENTORS [27-06-2020(online)].pdf | 2020-06-27 |
| 8 | 201941025908-Correspondence_Form2-Form3-Form5 and Specification_03-09-2020.pdf | 2020-09-03 |
| 8 | 201941025908-DRAWING [27-06-2020(online)].pdf | 2020-06-27 |
| 9 | 201941025908-COMPLETE SPECIFICATION [27-06-2020(online)].pdf | 2020-06-27 |
| 10 | 201941025908-DRAWING [27-06-2020(online)].pdf | 2020-06-27 |
| 10 | 201941025908-Correspondence_Form2-Form3-Form5 and Specification_03-09-2020.pdf | 2020-09-03 |
| 11 | 201941025908-FORM 18 [08-06-2023(online)].pdf | 2023-06-08 |
| 11 | 201941025908-ENDORSEMENT BY INVENTORS [27-06-2020(online)].pdf | 2020-06-27 |
| 12 | 201941025908-FORM 3 [27-06-2020(online)].pdf | 2020-06-27 |
| 12 | 201941025908-FER.pdf | 2024-08-12 |
| 13 | Correspondence by Applicant_Form 1_15-07-2019.pdf | 2019-07-15 |
| 13 | 201941025908-FER_SER_REPLY [12-02-2025(online)].pdf | 2025-02-12 |
| 14 | Form 1_After Filing_15-07-2019.pdf | 2019-07-15 |
| 14 | 201941025908-CLAIMS [12-02-2025(online)].pdf | 2025-02-12 |
| 15 | 201941025908-DRAWINGS [28-06-2019(online)].pdf | 2019-06-28 |
| 15 | 201941025908-ABSTRACT [12-02-2025(online)].pdf | 2025-02-12 |
| 16 | 201941025908-PatentCertificate17-02-2025.pdf | 2025-02-17 |
| 16 | 201941025908-FORM 1 [28-06-2019(online)].pdf | 2019-06-28 |
| 17 | 201941025908-PROVISIONAL SPECIFICATION [28-06-2019(online)].pdf | 2019-06-28 |
| 17 | 201941025908-IntimationOfGrant17-02-2025.pdf | 2025-02-17 |
| 1 | 201941025908_SearchE_03-07-2024.pdf |