Ketoprofen → Dexketoprofen

(±)-2-(3-Benzoylphenyl)propionic acid (51 g, 0.2 mol) was dissolved in MIBK (290 ml) and (S)-(+)-3-methyl-2-phenylbutylamine (19.6 g, 0.12 mol) was added dropwise with stirring. After completing the addition, the reaction solution was maintained at 35° C. to 40° C. for one hour and stirred at room temperature for 5 hours and then at 10° C. for 3 hours. Then, the crystal precipitated was filtered and the filter cake was washed with cold MIBK (70 ml) to give a wet cake (67 g). To this wet cake was added MIBK (240 ml) and the mixture was heated to dissolve at 77° C. Then, the mixture was cooled and stirred at 10° C. for 2 hours. Then, the crystal precipitated was filtered to give a diastereomer salt (30.2 g) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine. This diastereomer salt was treated with hydrochloric acid to give (S)-(+)-2-(3-benzoylphenyl)propionic acid (18.26 g). The optical purity of this propionic acid was 99.2% e.e. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 71.6% e.e.

1. additionthe addition
2. temperaturethe reaction solution was maintained at 35° C. to 40° C. for one hour
3. stirringstirred at room temperature for 5 hours
4. customThen, the crystal precipitated
5. filtrationwas filtered
6. washthe filter cake was washed with cold MIBK (70 ml)
7. customto give a wet cake (67 g)
8. temperaturethe mixture was heated
9. dissolutionto dissolve at 77° C
10. temperatureThen, the mixture was cooled
11. stirringstirred at 10° C. for 2 hours
12. customThen, the crystal precipitated
13. filtrationwas filtered

ORD 기록

ord-f6992c1874c943c9bfed1215cd8530a7

출처 데이터셋

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05852209