ChemicalBook CAS DataBase List Fluoxetine hydrochloride

Fluoxetine hydrochloride synthesis

8synthesis methods

Product Name:Fluoxetine hydrochloride
CAS Number:56296-78-7
Molecular formula:C17H19ClF3NO
Molecular Weight:345.79

A method for the synthesis of fluoxetine hydrochloride was developed by the Mannich reaction of acetophenone with methylamine hydrochloride, paraformaldehyde to form 3-methylamino-1-phenylacetic acid hydrochloride, followed by the preparation of 3-methylamino-I-phenylpropanol in methanol with potassium borohydride reductant, followed by etherification and salt formation to synthesize the antidepressant fluoxetine monohydrochloride.
Synthesis of Fluoxetine

Fluoxetine is the active ingredient in the antidepressant Prozac. It works as a selective serotonin reuptake inhibitor to treat conditions including depression and obsessive-compulsive disorder. To assemble this molecule, a three-step synthesis was utilized. Intermediates included 1- propanone, 3-(methylamino)-1-phenyl-(synthesized through an SN2 reaction between 3-chloropropiophenone and methylamine) and α-[2- (methylamino) ethyl] benzyl alcohol (synthesized through reduction of the first intermediate using NaBH4). The second intermediate was subjected to 4-chlorobenzotrifluoride and sodium hydride to produce the desired molecule, fluoxetine.

42142-52-9 Synthesis

42142-52-9
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455-13-0 Synthesis

455-13-0
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56296-78-7
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Yield:-

Reaction Conditions:

Stage #1: 3-methylamino-1-phenylpropan-1-ol;4-Iodobenzotrifluoridewith caesium carbonate;copper(I) bromide in xylenes at 130; for 16 h;
Stage #2: with hydrogenchloride in tert-butyl methyl ether;isopropyl alcohol;xylenes at 20;

Steps:

4 EXAMPLE 4

A mixture of N-methyl-3-hydroxy-3-phenylpropylamine (1.65 g, 10 mmol), 4-iodobenzotrifluoride (3.25 g, 12 mmol), cuprous bromide (0.17 g), cesium carbonate (3.9 g, 12 mmol) and xylenes (1 mL) was stirred under nitrogen at 130° C. until reaction completion as determined by ¹H NMR (16 hours). The reaction mixture was cooled to room temperature, diluted with methyl t-butyl ether (20 mL), filtered, and rinsed with more methyl t-butyl ether. 20% HCl solution in isopropanol (3 mL) was added and the resulting solution was evaporated to dryness to yield a solid residue. The residue was stirred with methyl t-butyl ether (20 mL) for 1 hour at room temperature and the suspension was filtered and washed with more methyl t-butyl ether to give 2.4 g of N-methyl-3-(4-trifluoromethylphenoxy)-3-phenylpropylamine hydrochloride (Fluoxetine hydrochloride) as a white solid. ¹H NMR spectrum of the product is identical to that of Example 3.

References:

US2007/10678,2007,A1 Location in patent:Page/Page column 7

42142-52-9 Synthesis

42142-52-9
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98-56-6 Synthesis