1-Fluoronaphthalene → Duloxetine

HRID 41610

反応式

HRID 41610 の反応式
[CH3:1][NH:2][CH2:3][CH2:4][C@@H:5]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[OH:6].F[C:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:16]=[CH:15][CH:14]=1.CC(C)([O-])C.[K+]>CS(C)=O>[CH3:1][NH:2][CH2:3][CH2:4][C@H:5]([O:6][C:21]1[CH:20]=[CH:19][CH:18]=[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:22]=12)[C:7]1[S:8][CH:9]=[CH:10][CH:11]=1

参加物

5

反応物 3

HCID 94501-FluoronaphthaleneHCID 100950473-(N-Methylamino)-1-(2-thienyl)-1-propanol, (-)-HCID 23665647Potassium tert-butoxide

生成物 1

HCID 60835Duloxetine

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
60 °C

実験手順

(S)-(−)-3-methylamino-1-(2-thienyl)-propan-1-ol (20.0 g) and 1-fluoronaphthalene (68.3 g) were charged into a 4-neck round bottomed flask. Potassium tert-butoxide (13.1 g) and DMSO (36.0 g) were then added, and the resulting mixture was heated to 60° C. for 8 hours. After completion of the reaction, the reaction mixture was cooled down and washed with water. Layers were separated, and the organic layer was further extracted with 32% HCl(aq) (14.7 g) to separate Duloxetine® from 1-floronaphthalene. The acidic aqueous layer was adjusted to pH 12-13 with 45% NaOH(aq) (17.6 g) to obtain Duloxetine® in a free base form as an oily liquid (31.3 g, 90%). Optical purity of the resulting Duloxetine® measured by chiral HPLC was 95% e.e.

後処理

  1. customAfter completion of the reaction
  2. temperaturethe reaction mixture was cooled down
  3. washwashed with water
  4. customLayers were separated
  5. extractionthe organic layer was further extracted with 32% HCl(aq) (14.7 g)
  6. customto separate Duloxetine® from 1-floronaphthalene

出典と根拠

ORDレコード
ord-c03510cd2eef4182a781137295957622
出典データセット
uspto-grants-2013_09
特許番号
US08530674B2

関連ノート

読み込み中…