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

HRID 41607

Reaction equation

HRID 41607 reaction equation
[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

Participants

4

Reactant 2

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

Product 1

HCID 60835Duloxetine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

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.

Sources & evidence

ORD record
ord-955aa3d7d65441f1ae52b8733f05aa6d
Source dataset
uspto-grants-2013_09
Patent number
US08530674B2

Linked notes

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