Process for preparation of high-purity meloxicam and meloxicam potassium salt
a technology of meloxicam and potassium salt, which is applied in the field of preparation of high-purity meloxicam and meloxicam potassium salt, can solve the problems of toxic and costly solvents, halogenated organic solvents that require extensive analytical testing, and harmful to the environment, and achieves high purity
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example 1
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide potassium salt monohydrate (compound of the Formula I)
[0055]350 ml of xylene are transferred into an apparatus equipped with Marcusson head and provided with means for inert gas purging. Purging with argon is started and 35.0 g (130 mmol) 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid methylester of the Formula (III) [wherein the meaning of R is methyl], 15.0 g (132 mmol) of 2-amino-5-methyl-thiazole of the Formula (IV) and 6.0 g of activated carbon are added during continous stirring and argon purge.
[0056]The reaction mixture is heated for 24 hours using an oil bath at a temperature between 170 and 180° C. The heating is adjusted in a way that only a minimal amount of distillate (2-5 ml / hour) is produced in the head. Distillation of methanol is ceased by the end of the reaction.
[0057]The reaction mixture is cooled to 25° C., crude meloxicam containing carbon and approximately 12% o...
example 2
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide (compound of Formula (II), polymorph I form of meloxicam
[0065]34.1 g (83.7 mmol) meloxicam potassium salt monohydrate are dissolved in the mixture of 1500 ml of 0.5% aqueous potassium hydroxide solution and 25 ml of ethanol at the temperature of 40-45° C. by stirring for 30 minutes. The yellow solution are added 2.0 g of activated carbon and after stirring for ten minutes, the carbon is filtered off. The filtrate are added 100 ml aqueous hydrochloric acid solution prepared by diluting 20 ml (23.6 g) concentrated hydrochloric acid to 100 ml final volume, at 30° C. in 30 minutes (pH 3-5). The suspension is stirred for two hours at 10° C. temperature, filtered and the product is washed on the filter with water.
[0066]Yield: 28.5 g (97.1% calculated on the basis of the weight of meloxicam potassium salt monohydrate as starting compound)
[0067]Melting point: 246-248° C.
[0068]Elemental analysis (C14H1...
example 3
4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine-3-carboxamide-1,1-dioxide potassium salt monohydrate (compound of the Formula (I))
[0070]One proceeds according to Example 1 with the difference that instead of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid methylester [compound of the Formula (III), wherein R is methyl)], 36.83 g (130 mmol) 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid ethylester [compound of the Formula (III), wherein R is ethyl] are used.
[0071]Yield: 46.9 g (88.5% calculated on the basis of the weight of the starting compound -hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid methylester of the Formula (III)).
[0072]Content (on the basis of potassium content): 99.6%
[0073]Water (Karl Fischer method): 4.7%
[0074]Elemental analysis [C14H12KN3O4S2.H2O (407,5)]
CalculatedC: 41.26H: 3.46N: 10.31S: 15.74MeasuredC: 41.22H: 3.38N: 10.25S: 15.69
[0075]Purity (HPLC): 99.8%.
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