3-(N-Methylamino)-1-(2-thienyl)-1-propanol, (-)- → Duloxetine

HRID 41607노트

반응식

HRID 41607 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].[CH3:12][C:13]([CH3:16])([O-])[CH3:14].[K+]>CS(C)=O>[CH3:1][NH:2][CH2:3][CH2:4][C@H:5]([O:6][C:3]1[C:16]2[C:13](=[CH:14][CH:9]=[CH:10][CH:11]=2)[CH:12]=[CH:5][CH:4]=1)[C:7]1[S:8][CH:9]=[CH:10][CH:11]=1

참가 물질

4

반응물 2

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

생성물 1

HCID 60835Duloxetine

시약·촉매·용매 1

HCID 679Dimethyl Sulfoxide용매

실험 절차

In the step (iv) of the process of the present invention, the reaction of (S)-(−)-3-methylamino-1-(2-thienyl)propan-1-ol and halonaphthalene is carried out by using a proper base such as potassium tert-butoxide in a suitable amount of DMSO to form (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine (Duloxetine®). The excess amount of halonaphthalene, ranging from about 1.5 to 4 equivalents, can be recovered. The reaction is performed at a temperature ranged from 20° C. to 110° C., preferably from 40° C. to 90° C., for 1 to 24 hours. One embodiment of the present invention is conducted in the presence of excess halonaphthalene and a suitable amount of DMSO to overcome the problems regarding racemization and environmental protection. In one preferred embodiment, DMSO is used in amounts ranging from one to ten times the amount of (S)-(−)-3-methylamino-1-(2-thienyl)propan-1-ol, more preferably from one to five times the amount of (S)-(+3-methylamino-1-(2-thienyl)propan-1-ol.

출처 및 근거

ORD 기록
ord-955aa3d7d65441f1ae52b8733f05aa6d
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08530674B2

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