Process for the preparation of zolmitriptan, salts and solvates thereof
A solvate and organic solvent technology, applied in the field of preparing zolmitriptan and its pharmaceutically acceptable salts and solvates, and preparing an active pharmaceutical ingredient zolmitriptan, can solve the problem of low yield and difficulty in scaling up industrial scale , low purity and other problems, to achieve the effect of high yield
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Embodiment 1
[0132] Embodiment 1-preparation of zolmitriptan (I)
[0133] (S)-4-(4-Aminbenzyl)-1,3-oxazolidin-2-one (IX) (100 g) was added to water (400 ml, 4.0 volumes) and concentrated HCl was added at 25-30 °C (200ml, 2.0 volumes). The solution was cooled to 5°C to -10°C and a solution of sodium nitrite (54 g, 1.5 eq) in water (400 ml, 4.0 vol) was added maintaining the temperature below -5°C. After the addition was complete, the reaction mixture was stirred for 3 hours resulting in formation of diazonium chloride (XV) in solution.
[0134] To a pre-dissolved stannous chloride solution (234.5 g, 2.0 equiv in 200 ml, 2.0 volumes of HCl) was slowly added a solution of diazonium chloride (XV) at 5°C-10°C. The mixture was stirred at 5°C-10°C for 4 hours. After completion of hydrazine formation (measured by TLC), the pH of the reaction mixture was adjusted from about pH 2 to pH 8-9 at 25°C to 30°C by using sodium carbonate (100 g) to generate (S)-4-(4- Hydrazinebenzyl)-1,3-oxazolidin-2-o...
Embodiment 2
[0144] Example 2 - Crystallization of Zolmitriptan (I)
[0145] Pure zolmitriptan (I) obtained above was crystallized from isopropanol as follows. Pure zolmitriptan (40.0 g) was dissolved in isopropanol (200 ml) at 45-50°C to give a clear solution. To the clear solution, Norit Supra B activated carbon (4.0 g, 10% w / w) was added and the mixture was heated at 45-50°C for 1 hour. The solution is then passed through the Celite Bed filter and concentrate the filtrate to about 100ml under reduced pressure. The resulting suspension was cooled to 0-5°C and stirred for 1 hour. The crystallized zolmitriptan (I) was filtered and dried at 45-50° C. under reduced pressure until a constant weight was obtained (about 6 hours).
[0146] Yield: 87% (w / w)
[0147] HPLC purity: 99.94%
[0148] By following similar experimental conditions, by using different solvents or mixtures of solvents such as methanol, ethanol, n-propanol, tert-butanol, pentanol, acetone, methyl ethyl ketone, diethyl...
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