1-Fluoronaphthalene → Duloxetine

HRID 41610

반응식

HRID 41610 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

HCID 60835Duloxetine

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

반응 조건

온도
60 °C

실험 절차

(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.

후처리

  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

출처 및 근거

ORD 기록
ord-c03510cd2eef4182a781137295957622
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530674B2

연결된 노트

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