1-Chloro-4-(trifluoromethyl)benzene → Fluoxetine

HRID 374358Notes

Reaction equation

HRID 374358 reaction equation
[C:1]1([CH:7]([OH:12])[CH2:8][CH2:9][NH:10][CH3:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1.CN1CCCC1=O.CC(C)([O-])C.[K+]>CS(C)=O>[CH3:11][NH:10][CH2:9][CH2:8][CH:7]([O:12][C:14]1[CH:19]=[CH:18][C:17]([C:20]([F:23])([F:22])[F:21])=[CH:16][CH:15]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 73941-Chloro-4-(trifluoromethyl)benzeneHCID 13387N-methyl-2-pyrrolidoneHCID 27339893-Methylamino-1-phenylpropanolHCID 23665647Potassium tert-butoxide

Product 1

HCID 3386FluoxetineYield 85%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

An improved process for the preparation in a superior yield of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine of formula (I), ##STR5## or a pharmaceutically acceptable acid addition salt thereof, the said process comprising catalytically hydrogenating 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base of formula (II), ##STR6## to obtain 1-phenyl-3-(N-methylamino)-propan-1-ol of formula (III), ##STR7## and selectively etherifying the compound of formula (III) with 1-chloro-4-trifluoromethylbenzene of formula (IV), ##STR8## in a solvent selected from the group consisting of N-methylpyrrolidone and dimethylsulfoxide in the presence of a potassium t-butoxide, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine is formed in a yield greater than 85 percent of the theoretical value.

Sources & evidence

ORD record
ord-32369cdc0c994fb6a8166350ef0c5a7f
Source dataset
uspto-grants-1992_11
Patent number
US05166437

Reaction notes

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