114446-50-3

Usage

Chemical Properties

Pale Yellow Oil

InChI:InChI=1/C16H17ClO/c1-13-7-5-6-10-15(13)18-16(11-12-17)14-8-3-2-4-9-14/h2-10,16H,11-12H2,1H3/t16-/m0/s1

Upstream product

• 95-48-7 ortho-cresol 
• 100306-33-0 (1R)-3-chloro-1-phenylpropanol 
• 18776-12-0 3-chloro-1-phenyl-propan-1-ol 
• 141987-54-4 1-Phenyl-3-chlor-propyl-monochloracetat 
• 936-59-4 3-chloropropiophenone 

Downstream Products

• 82857-39-4 -(+)-tomoxetine hydrochloride 
• 105314-53-2 (S)-N-methyl-3-(2-methylphenoxy)-3-phenyl-1-propanamine 

Relevant academic research and scientific papers

Chemoenzymatic synthesis of the non-tricyclic antidepressants Fluoxetine, Tomoxetine and Nisoxetine

3-Chloro-1-phenylpropan-1-ol and the corresponding butanoate, 3-chloro-1-phenyl-1-propyl butanoate, were kinetically resolved using lipase B from Candida antarctica catalysis by transesterification and hydrolysis respectively. The resulting chiral building blocks (S)- and (R)-3-chloro-1-phenylpropanol were converted into both enantiomers of the antidepressant drugs, Fluoxetine, Tomoxetine and Nisoxetine. The Royal Society of Chemistry 2000.

Hydrolases in organic synthesis: Preparation of enantiomerically pure compounds

Esterhydrolases (Esterases, Lipases) are highly (chemo-, regio- and enantio-) selective biocatalysts for the transformation of racemic and achiral substrates into enantiomerically pure compounds.Numerous examples for their application in the preparation of synthetically useful chiral auxiliaries and building blocks for flavour compounds, pheromones and several pharmaceuticals including β-adrenergic blockers, antidepressants and ACE inhibitors are presented.

An efficient route to enantiomerically pure antidepressants: Tomoxetine, nisoxetine and fluoxetine

Both enantiomers (R)- and (S)-3-chloro-1-phenyl-1-propanol can be obtained conveniently by an efficient enzymatic resolution process. They can be converted via enantioconvergent routes into all enantiomers of the important antidepressants (R)- and (S)-Tomoxetine, Fluoxetine and Nisoxetine.

Iodinated tomoxetine derivatives as selective ligands for serotonin and norepinephrine uptake sites

In order to develop selective radioactive ligands for the study of presynaptic monoamine uptake sites, iodinated derivatives of tomoxetine were synthesized and evaluated in radioligand binding assays. Iodotomoxetine derivatives showed high affinity for serotonin (5-HT) uptake sites using a rat cortical membrane preparation. Compound 1R, (R)-(-)-N-methyl-3-(4-iodo-2- methyl]phenoxy)-3-phenylpropanamine, was the most potent and showed high stereoselectivity for 5-HT uptake sites (K(i), R isomer = 0.65 nM, S isomer = 13.9 nM). Changing the position of the methyl group or eliminating the methyl group at the phenoxy ring resulted in a loss of stereoselectivity. Substitution of the methyl group of tomoxetine with iodine gave the R and S isomers of N-methyl-3-(2-iodophenoxy)-3-phenylpropanamine 4R and 4S. These compounds displayed stereoselectivity for the norepinephrine (NE) (K(i) values = 0.24 and 9.35 nM for R and S isomers, respectively). The in vitro binding data suggest that 1R and 4R are potential radioiodinated ligands for pharmacological studies of 5-HT and NE uptake sites, respectively.

Novel process of producing phenyl or substituted phenylalkylamine pharmaceutical agents and novel chiral intermediates of high enantiomeric purity useful therein

A process for producing the optically pure (+)- or (-) isomer of a phenyl- or substituted- phenylalkanolamine compounds having pharmacologic activity without the need for resoltuion processes ad novel intermediates useful in the process including optically pure haloalcohols are provided.

Chiral Synthesis via Organoboranes. 18. Selective Reductions. 43. Diisopinocampheylchloroborane as an Excellent Chiral Reducing Reagent for the Synthesis of Halo Alcohols of High Enantiomeric Purity. A Highly Enantioselective Synthesis of Both Optical Isomers of Tomoxetine, Fluoxetine, a

Diisopinocampheylchloroborane, dIpc2BCl, reduces ring and chain sustituted haloaralkyl ketones to the corresponding halo alcohols in excellent enantiomeric excess.In certain cases these alcohols can be upgraded by simple methods to essentially 100percent ee.For instance, (+)- or (-)-3-chloro-1-phenyl-1-propanol is initially obtained in 97percent ee.Simple recrystallisation then furnishes the pure enantiomers.These chiral halo alcohols are highly versatile intermediates.They can be readily cyclized to oxiranes and 2-substituted tetrahydrofurans with retention of chirality.Utilizing this methodology, we have developed an efficient, highly enantioselective synthesis of both optical isomers of the antidepressant drugs, Tomoxetine, Fluoxetine, and Nisoxetine, from the common intermediates (+)-or (-)-3-chloro-1-phenyl-1-propanol.