76183-10-3

Upstream product

• 2757-10-0 N-methylcinnamamide 
• 5764-85-2 Ethyl 3-hydroxy-3-phenylpropanoate 
• 1375257-32-1 (S)-3-[(S)-3-hydroxy-3-phenylpropanoyl]-4-isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one 
• 74-89-5 methylamine 
• 614-27-7 methyl 3-oxo-3-phenylpropionate 
• 197852-01-0 N-methyl-3-oxo-3-phenylpropanamide 
• 33401-74-0 ethyl (3R)-3-hydroxy-3-phenylpropionate 
• 100-52-7 benzaldehyde 
• 7449-74-3 N-methyl-N-trimethylsilylacetamide 
• 942-64-3 2-methyl-5-phenyl-isoxazol-3-one 

Downstream Products

• 82248-59-7 atomoxetine hydrochloride 
• 114247-06-2 (S)-fluoxetine hydrochloride 
• 114247-09-5 (R)-fluoxetine hydrochloride 
• 134619-79-7 (+)-N-tert-butoxycarbonyl-N-methyl-3-phenyl-3-<4-(trifluoromethyl)phenoxy>propanamine 
• 134619-78-6 (-)-N-tert-butoxycarbonyl-N-methyl-3-phenyl-3-(2-methylphenoxy)propanamine 
• 134619-77-5 (-)-N-tert-butoxycarbonyl-N-methyl-3-phenyl-3-hydroxypropylamine 
• 100568-02-3 (S)-fluoxetine 
• 54910-89-3 (R)-fluoxetine 
• 114133-37-8 (S)-N-methyl-3-amino-1-phenyl-1-propanol 

Relevant academic research and scientific papers

Access to optically pure β-hydroxy esters via non-enzymatic kinetic resolution by a planar-chiral DMAP catalyst

The development of new approaches to obtain optically pure β-hydroxy esters is an important area in synthetic organic chemistry since they are precursors of other high value compounds. Herein, the kinetic resolution of racemic β-hydroxy esters using a planar-chiral DMAP derivative catalyst is presented. Following this procedure, a range of aromatic β-hydroxy esters was obtained in excellent selectivities (up to s = 107) and high enantiomeric excess (up to 99% ee). Furthermore, the utility of the present method was demonstrated in the synthesis of (S)-3-hydroxy-N-methyl-3-phenylpropanamide, a key intermediate for bioactive molecules such as fluoxetine, tomoxetine or nisoxetine, in its enantiomerically pure form.

Reversal of selectivity in acetate aldol reactions of N-acetyl-(S)-4- isopropyl-1-[(R)-1-phenylethyl]imidazolidin-2-one

Synergistic effects of the exo- and endocyclic chiral centers of an imidazolidinone-based auxiliary were investigated in the perspective of acetate aldol reactions. The reversal in diastereoselectivity was accomplished by lithium and titanium enolate reactions, which proceed through proposed open and closed transitions states, respectively. The aldol adducts were used in the stereoselective synthesis of fluoxetine.

Copper-Catalyzed conjugate addition of diboron reagents to α,β-unsaturated amides: Highly reactive copper-1,2- bis(diphenylphosphino)benzene catalyst system

An efficient copper catalyst system for the β-boration of α,β-unsaturated amides has been developed. Copper-bisphosphine complexes with small bite angles generate efficient catalyst systems for the successful conjugate addition of bis(pinaco-lato)diboron

Enantioselective hydrogenation of β-ketoesters using a MeO-PEG-supported Biphep ligand under atmospheric pressure: A practical synthesis of (S)-fluoxetine

The preparation of a novel chiral 2,2′-bis(MeO-PEG-supported)-6, 6′-bis(diphenylphosphanyl)biphenyl (MeO-PEG-Biphep) ligand is described. The derived ruthenium complex catalyzes the hydrogenation of β-ketoesters in up to 99% yield and 99% ee under atmospheric pressure. The accelerating effects exerted by the PEG linkage are dramatic when compared to the unsupported analogue, MeO-Biphep-RuBr2. Furthermore, the catalyst can be recovered easily and the recycled catalysts were shown to maintain their efficiency in two consecutive runs, albeit with declining activity. One of the products, (S)-ethyl-3-hydroxy-3-phenylpropanoate, is useful in the preparation of (S)-fluoxetine. Georg Thieme Verlag Stuttgart.

Ru-SYNPHOS and Ru-DIFLUORPHOS: Highly efficient catalysts for practical preparation of β-hydroxy amides

Ru-SYNPHOS and Ru-DIFLUORPHOS catalysts were efficiently used for the synthesis of a wide variety of chiral β-hydroxy amides via asymmetric hydrogenation of the corresponding β-keto amides. Georg Thieme Verlag Stuttgart.

Preparation of polymer-supported Ru-TsDPEN catalysts and use for enantioselective synthesis of (S)-fluoxetine

Polymer-supported chiral ligands 9 and 17 were prepared based on Noyori's (1S,2S)- or (1R,2R)-N-(p-tolylsulfonyl)-1,2-diphenylethylenediamine. The combination with [RuCl2(p-cymene)]2 has been shown to exhibit high activities and enantioselectivities for heterogeneous asymmetric transfer hydrogenation of aromatic ketones (19a-c) with formic acid-triethylamine azeotrope as the hydrogen donor, whereby affording the respective optically active alcohols 20a-c, the key precursors of chiral fluoxetine. As exemplified by ligand 17 for substrate 19c, the catalysts can be recovered and reused in three consecutive runs with no significant decline in enantioselectivity. The procedure avoids the plausible contamination of fluoxetine by the toxic transition metal species. The Royal Society of Chemistry 2005.

The synthesis of a chiral fluoxetine intermediate by catalytic enantioselective hydrogenation of benzoylacetamide

In the presence of a chiral BINAP-ruthenium(II) catalyst, asymmetric hydrogenation of β-keto propanoic acid N-methyl amide under 200 psi of hydrogen pressure furnished the corresponding 3-hydroxypropanoic acid N- methyl amide as the single enantiomer. The

A novel chemoenzymatic enantioselective synthesis of some clinically effective CNS drugs and related compounds

We have demonstrated in this study a novel route for the synthesis of benzothiopyran and benzothiazepin ring systems along with the synthesis of optically pure, clinically effective drugs tomoxetine, fluoxetine and thiazesim.

A new chemoenzymatic enantioselective synthesis of R-(-)-tomoxetine, (R)- and (S)-fluoxetine

A new chemoenzymatic synthesis of optically pure (R)-Tomoxetine and both the enantiomers of Fluoxetine starting from (S)-ethyl-3-hydroxy-3-phenyl propionate obtained by enzymatic methods, is described.

Process for the preparation of fluoxetine hydrochloride

A process for the preparation of fluoxetine hydrochloride in which ethyl benzoylacetate is reduced to ethyl 3-hydroxy-3-phenyl propionate (X), compound (X) is treated with methylamine to obtain 3-hydroxy-3--phenyl propionic acid N-methyl amide (XI), compound (XI) is treated with 4-trifluoro methylphenol to obtain 3-phenyl-3-[4--(trifluoromethyl)phenoxy]N-methyl propanamide (XII) and compound (XII) is reduced to obtain fluoxetine from which, by treatment with HCl, fluoxetine hydrochloride is obtained.