Ketoprofen → Dexketoprofen

HRID 1459046

反応式

HRID 1459046 の反応式
[C:1]([C:9]1[CH:10]=[C:11]([CH:15]([CH3:19])[C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.COC(C)(C)C.CC(C)[C@@H](C1C=CC=CC=1)CN>O>[C:1]([C:9]1[CH:10]=[C:11]([C@H:15]([CH3:19])[C:16]([OH:18])=[O:17])[CH:12]=[CH:13][CH:14]=1)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 3

HCID 3825KetoprofenHCID 15413tert-Butyl methyl etherHCID 10176271(S)-3-Methyl-2-phenylbutylamine2 回

生成物 1

HCID 667550Dexketoprofen収率 37.6%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
10 °C

実験手順

To (±)-2-(3-benzoylphenyl)propionic acid (1200 g, 4.719 mol) were added methyl-t-butyl ether (hereinafter abbreviated to "MTBE") (4.8 L) and water (600 g, water/KET=0.50) and the mixture was dissolved with heating. Then, (S)-(+)-3-methyl-2-phenylbutylamine (388 g, 2.377 mol) was added dropwise with stirring at 50° C. to 55° C. This reaction solution was cooled to precipitate a crystal and then reheated from 35° C. to 50° C. This solution was again cooled and then reheated from 40° C. to 45° C. This solution was cooled slowly to 10° C. and stirred at 5° C. to 10° C. for one hour. Then, the crystal precipitated was filtered, and the filter cake was washed three times with cold MTBE (1 L) and dried. In this manner, a diastereomer salt (741 g, 1.775 mol) of (S)-(+)-2-(3-benzoylphenyl)propionic acid with (S)-(+)-3-methyl-2-phenylbutylamine was obtained. The yield of the product based on (S)-(+)-2-(3-benzoylphenyl)propionic acid contained in the starting material was 75.2% and the optical purity was 99.1% e.e.

後処理

  1. dissolutionthe mixture was dissolved
  2. temperaturewith heating
  3. temperatureThis reaction solution was cooled
  4. customto precipitate a crystal
  5. customreheated from 35° C. to 50° C
  6. temperatureThis solution was again cooled
  7. customreheated from 40° C. to 45° C
  8. stirringstirred at 5° C. to 10° C. for one hour
  9. customThen, the crystal precipitated
  10. filtrationwas filtered
  11. washthe filter cake was washed three times with cold MTBE (1 L)
  12. customdried

出典と根拠

ORDレコード
ord-8d08a3aac40e4298a777f7c845a403bb
出典データセット
uspto-grants-1998_12
特許番号
US05852209

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