CRYSTALLINE POLYMORPH OF AMINOETHYLPHENOXYACETIC ACID DERIVATIVE

摘要

THE PRESENT INVENTION RELATES TO A CRYSTALLINE POLYMORPH OF 2-[4-[2-[[(1S,2R)-2-HYDROXY-2-(4-HYDROXY-PHENYL)-1-METHYLETHYL]AMINO]ETHYL]PHENOXY]ACETIC ACID HAVING STRONG DIFFRACTION PEAKS (DIFFRACTION ANGLE : 2 0 ± 0.1°) AT 10.8, 19.1, 19.3, 19.8, 20.6, AND 27.0° IN POWDER X-RAY DIFFRACTION PATTERN, WHICH HAS POTENT ß2- AND ß3- ADRENOCEPTOR STIMULATING EFFECTS AND IS USEFUL AS AN AGENT FOR RELIEVING PAIN AND PROMOTING THE REMOVAL OF CALCULI IN UROLITHIASIS. THE CRYSTALLINE POLYMORPH CAN BE PREPARED BY HYDROLYZING ETHYL 2-[4-[2-[[(1S,2R)-2-HYDROXY-2-(4-HYDROXY-PHENYL)-1-METHYLETHYL]AMINO]ETHYL]PHENOXYL]ACETATE PHOSPHATE BY SODIUM HYDROXIDE, ADDING AN AQUEOUS PHOSPHORIC ACID SOLUTION AT 40°C AND OVER, COLLECTING THE RESULTING 2-[4--[2-[[(1S, 2R)-2-HYDROXY-2-(4-HYDROXYPHENYL)-1-METHYLETHYL]-AMINO]ETHYL]PHENOXYL]ACETATE ACID BY FILTRATION, ADDING A MIXED SOLVENT OF WATER AND METHANOL OR METHANOL TO THE WET SOLID, AND STIRRING THE SUSPENSION AT 40°C TOREFLUX TEMPERATURE FOR 30 MINUTES TO SEVERAL HOURS.