D-Tartaric acid → Traxoprodil

HRID 479578

反応式

HRID 479578 の反応式
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([OH:24])[CH:9]([N:11]2[CH2:16][CH2:15][C:14]([OH:23])([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:13][CH2:12]2)[CH3:10])=[CH:4][CH:3]=1.[C:25]([OH:34])(=[O:33])[C@H:26]([C@@H:28]([C:30]([OH:32])=[O:31])[OH:29])[OH:27]>CO>[C:30]([C@H:28]([C@@H:26]([C:25]([O-:34])=[O:33])[OH:27])[OH:29])([O-:32])=[O:31].[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([OH:24])[C@@H:9]([N:11]2[CH2:12][CH2:13][C:14]([OH:23])([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:15][CH2:16]2)[CH3:10])=[CH:4][CH:3]=1

参加物

5

反応物 2

HCID 439655D-Tartaric acidHCID 100650201-[(1s,2s)-2-Hydroxy-2-(4-hydroxyphenyl)-1-methylethyl]-4-phenylpiperidin-4-ol

生成物 2

HCID 219101Traxoprodil収率 62.1%HCID 5460284D-Tartrate

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
52.5 °C

実験手順

To an appropriate flask maintained under a nitrogen atmosphere, 1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol (189.5 g, 0.58 mol) and methanol (3.8 L) were added. The mixture was heated to 50-55° C. and then D-(−)-tartaric acid (87.0 g , 0.58 mol) was added. The mixture was heated at reflux (˜65° C.) for 5 hours. The slurry was cooled at 30-35° C. and then granulated for 1 hour at 30-35° C. The product was filtered and the cake was washed with fresh methanol (135 mL). The wet cake was sampled for a chiral HPLC assay to determine enantiomeric impurity levels. The wet cake was suspended in methanol (1.6 L), and the resulting slurry was heat at reflux (˜65° C.) under a nitrogen atmosphere for 5 hours. The slurry was cooled to 30-35° C., granulated for 1 hour at 30-35° C. and then filtered. The filter cake was washed with methanol (136 mL) and then dried in vacuo at 40-45° C. for 18-24 hours. A sample was assayed by chiral HPLC. The D-(−)-tartrate salt of (1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidin-1-yl)-1-propanol (118.0 g) was obtained in 43% weight yield. At times, as the results show in Table 1 above an additional methanol reslurry is required to decrease the amount of the (1R,2R)-enantiomer impurity below 2.5%.

後処理

  1. temperatureTo an appropriate flask maintained under a nitrogen atmosphere
  2. temperatureThe mixture was heated
  3. temperatureat reflux (˜65° C.) for 5 hours
  4. temperatureThe slurry was cooled at 30-35° C.
  5. filtrationThe product was filtered
  6. washthe cake was washed with fresh methanol (135 mL)
  7. aliquotThe wet cake was sampled for a chiral HPLC assay
  8. temperaturethe resulting slurry was heat
  9. temperatureat reflux (˜65° C.) under a nitrogen atmosphere for 5 hours
  10. temperatureThe slurry was cooled to 30-35° C.
  11. waitgranulated for 1 hour at 30-35° C.
  12. filtrationfiltered
  13. washThe filter cake was washed with methanol (136 mL)
  14. customdried in vacuo at 40-45° C. for 18-24 hours

出典と根拠

ORDレコード
ord-07dfbe0090544da49b0b54655711d974
出典データセット
uspto-grants-2003_11
特許番号
US06645986B2

関連ノート

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