Abstract: ABSTRACT The present invention relates to an improved process for the preparation of 4-amino-5-hexenoic acid (1) with purity greater than 99.0% by HPLC.
We claim:
1. A process for the preparation of Vigabatrin (1) having purity greater
than 99.0% comprising:
a) reaction of l,4-dichlorobut-2-ene (2) with diethyl malonate (3) in the presence of a base to form diethyl 2-vinylcyclo propane-1,1-dicarboxylate (4);
b) ammonolysis of 2-vinylcyclo propane-1,1-dicarboxylate (4) in an organic solvent to form 2-oxo-5-vinylpyrrolidine-3-carboxamide (5); and
c) hydrolysis of 2-oxo-5-vinylpyrrolidine-3-carboxamide (5) in the presence of acid to form Vigabatrin (1).
2. The process according to claim 1, wherein the base used in step a) is selected from tri ethylamine, sodium methoxide and sodium ethoxide.
3. The process according to claim 1, wherein the organic solvent used in step b) is selected from methanol, ethanol, isopropanol, dimethyl formamide, formamide, N-methyl formamide or mixtures thereof.
4. The process according to claim 1, wherein the acid used in step c) is selected from hydrochloric acid, hydrobromic acid, methane sulfonic acid, toluene sulfonic acid and trifluoro acetic acid.
5. A process for the purification of Vigabatrin (1), which comprising:
a) providing a solution of Vigabatrin (1) in a solvent or mixture of solvents;
b) heating the reaction mixture to a suitable temperature;
c) optionally, treating with neutral charcoal;
d) adding a protic solvent; and
e) isolating pure Vigabatrin (1).
6. The process according to claim 5, wherein solvent used is selected
from methanol, ethanol, isopropanol, water, dimethyl formamide,
formamide, N-methyl formamide or mixtures thereof.
7. The process according to claim 5, wherein step b) is carried out at a temperature of 40-60 °C and preferably 50-60 °C
8. The process according to claim 1, wherein Vigabatrin obtained is having purity grater than 99% and characterized by one or more of the following;
i. less than 0.10% of 5-vinylpyrrolidin-2-one (impurity A);
and ii. less than 0.10%) of 2-(2-aminobut-3-en-l-yl)malonic
acid (impurity E).
| # | Name | Date |
|---|---|---|
| 1 | 201841040963-PROVISIONAL SPECIFICATION [30-10-2018(online)].pdf | 2018-10-30 |
| 2 | 201841040963-FORM 1 [30-10-2018(online)].pdf | 2018-10-30 |
| 3 | 201841040963-DRAWINGS [30-10-2018(online)].pdf | 2018-10-30 |
| 4 | 201841040963-FORM FOR SMALL ENTITY [29-10-2019(online)].pdf | 2019-10-29 |
| 5 | 201841040963-FORM 3 [29-10-2019(online)].pdf | 2019-10-29 |
| 6 | 201841040963-EVIDENCE FOR REGISTRATION UNDER SSI [29-10-2019(online)].pdf | 2019-10-29 |
| 7 | 201841040963-ENDORSEMENT BY INVENTORS [29-10-2019(online)].pdf | 2019-10-29 |
| 8 | 201841040963-ENDORSEMENT BY INVENTORS [29-10-2019(online)]-1.pdf | 2019-10-29 |
| 9 | 201841040963-DRAWING [29-10-2019(online)].pdf | 2019-10-29 |
| 10 | 201841040963-COMPLETE SPECIFICATION [29-10-2019(online)].pdf | 2019-10-29 |
| 11 | Correspondence by Applicant_Form-2,FORM-5,Form-3_14-11-2019.pdf | 2019-11-14 |
| 12 | 201841040963-FORM 18 [17-10-2022(online)].pdf | 2022-10-17 |
| 13 | 201841040963-FER.pdf | 2022-11-03 |
| 14 | 201841040963-Proof of Right [03-05-2023(online)].pdf | 2023-05-03 |
| 15 | 201841040963-FER_SER_REPLY [03-05-2023(online)].pdf | 2023-05-03 |
| 16 | 201841040963-CLAIMS [03-05-2023(online)].pdf | 2023-05-03 |
| 17 | 201841040963-ABSTRACT [03-05-2023(online)].pdf | 2023-05-03 |
| 18 | 201841040963-Form 2(Title Page)-010923.pdf | 2023-10-05 |
| 19 | 201841040963 Form 7A Pre-grant opposition 010923.pdf | 2024-02-29 |
| 1 | SearchStrategy201841040963E_28-10-2022.pdf |