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

HRID 374359Notes

Reaction equation

HRID 374359 reaction equation
[H][H].[C:3]1([CH:9]([OH:14])[CH2:10][CH2:11][NH:12][CH3:13])[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl[C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1.CC(C)([O-])C.[K+]>C(OCC)(=O)C.[Pt].[Pd].[Pd].[Pt].CS(C)=O.CN1CCCC1=O>[CH3:13][NH:12][CH2:11][CH2:10][CH:9]([O:14][C:16]1[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

11

Reactant 4

HCID 73941-Chloro-4-(trifluoromethyl)benzeneHCID 27339893-Methylamino-1-phenylpropanol3×HCID 23665647Potassium tert-butoxideHCID 178418361HCID 178418361, compound

Product 1

HCID 3386FluoxetineYield 85%

Reagents, catalysts & solvents 6

HCID 23938PalladiumCatalystHCID 23939PlatinumCatalystHCID 56923625Palladium--platinum (1/1)CatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

An improved process for the preparation in a superior yield of the hydrochloride salt of N-methyl-3-(p-trifluoro-methylphenoxy)-3-phenylpropylamine of formula (I), ##STR9## said process comprising catalytically hydrogenating 2-benzoyl-1-(N-benzyl-N-methyl)ethylamine base of formula (II), ##STR10## with the aid of a catalyst selected from the group consisting of Pt/C, Pd/C and Pd-Pt/C in ethyl acetate at a hydrogen pressure of 1 to 20 bar and at a temperature of approximately 20° to 100° C. whereby 1-phenyl-3-(N-methylamino)-propan-1-ol of formula (III) is formed, ##STR11## and selectively etherifying the compound of formula (III) with 1-chloro-4-trifluoromethylbenzene of formula (IV), ##STR12## in a solvent selected from the group consisting of N-methylpyrrolidone and dimethylsulfoxide in the presence of potassium t-butoxide, whereby N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine is formed in a yield greater than 85 percent of the theoretical value and is converted to the hydrochloride salt.

Workup

  1. customis formed

Sources & evidence

ORD record
ord-3db2d2cfcc484cf4876ef3b9d4ac9f82
Source dataset
uspto-grants-1992_11
Patent number
US05166437

Reaction notes

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