反应详情

2-Methoxyethyl 4-hydroxy-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide (28 g., 0.089 mole) and 2-aminopyridine (9.26 g., 0.098 mole) were combined with 500 ml. of xylene in a 1 liter flask equipped with an addition funnel and a reflux, variable take-off distillation head. The stirred reaction mixture was heated to reflux and the xylene distilled at the rate of approximately 100 ml./hour, while maintaining the pot volume almost constant by the addition of fresh xylene. After 6 hours, the head temperature, which had been relatively constant at 134° C., rose to 142° C. and reflux rate slowed. The reaction mixture was then cooled in an ice-bath and the precipitated solids recovered by filtration, with hexane for transfer and wash, and dried at 45° C., in vacuo to yield piroxicam (28.5 g., 96%; m.p. 167°-174° C.). This product was examined by high performance liquid chromatography using 60:40 0.1 M Na2HPO4 adjusted to pH 7.5 with citric acid:methanol on Micro-Bonda pak C18 (Trademark of Waters Associates for a standard hplc column packing consisting of siloxy substituted silica coated on micro-glass beads). Under the conditions employed, piroxicam has a retention time of about 6 minutes, whereas the potential contaminant, O4 -methoxyethylpiroxicam, has a retention time of 16.5 minutes. None of the potential contaminant was detected in the product of the present Example.

1. distillationa reflux, variable take-off distillation head
2. customThe stirred reaction mixture
3. temperaturewas heated
4. temperatureto reflux
5. distillationthe xylene distilled at the rate of approximately 100 ml
6. temperature/hour, while maintaining the pot volume
7. additionalmost constant by the addition of fresh xylene
8. customhad been relatively constant at 134° C.
9. customrose to 142° C.
10. temperaturereflux rate
11. temperatureThe reaction mixture was then cooled in an ice-bath
12. filtrationthe precipitated solids recovered by filtration, with hexane for transfer
13. washwash
14. customdried at 45° C., in vacuo