3-phenylpropanenitrile

Then a THF (8mL) solution of 3-oxo-3-phenylpropanenitrile (1.0 mmol) was added at a rate of 3 mL h by a syringe pump. After the addition was complete, the mixture was allowed to cool down and treated with 10 mL methanol and filtered. The solid polymeric catalyst was washed several times with ethyl acetate and methanol. 

To a solution of non-purihed (7 )-3-amino-l-phenylpropan-l-ol which had been prepared from 3-oxo-3-phenylpropanenitrile (1.0 mmol) (see above) in 15 mL dichloromethane was added 10 mL saturated aqueous NaHCOa. Ethyl chloroformate (0.4 mL) in 15mL dichloromethane was added to the mixture dropwise over 10 min. The mixture was allowed to stir at room temperature overnight. 

The reaction mixture was extracted with dichloromethane (3 x 10 mL) and dried with anhydrous sodium sulfate. The solvent was evaporated and the residue was purihed by column chromatography employing ethyl acetate-hexane (10 90) as the eluent to afford (7 )-ethyl 3-hydroxy-3-phenylpropylcarbamate as an oil (63% yield over two steps from 3-oxo-3-phenylpropanenitrile). 

A Electrophilic substitution on 3-phenylpropanenitrile occurs at the ortho and para positions, but reaction with 3-j5henyIpropenenitrile occurs at the meta position. Explain, using resonance structures of the intermediates. 

The C = N-Ar moiety is similar in reactivity to the carbonyl function. Thus, 2-arylamino-3-oxo-3-phenylpropanenitriles react with benzene-1,2-diamine to give 3-substituted quinoxa-line-2-carbonitriles, e.g. 25, in nearly quantitative yield. ... 

Recently we determined that two R. rhodochrous strains (A29 and A99) expressed nitrilase activity after induction. These strains were capable of enantioselectively hydrolyzing racemic 3-amino-3-phenylpropanenitrile directly to the corresponding (R)-3-amino-3-phenylpropanoic acid with >95% ee (Table 14.1) in a kinetic resolution. Various inhibitors were used, that indicated the observed hydrolytic activity was due to the presence of a nitrilase rather than a nitrile hydratase and amidase pair [47]. 

A nice application in pharmaceutical s)mthesis has been reported. Thus, from the reduction of pentoxifylline a new methylxanthine could be obtained, and a high ee of 98% was observed for this transformation [126, 127]. Since the baker s yeast reduction of 3-oxo-3-phenylpropanenitrile has been difficult to achieve, a library of baker s yeast reductases was screened. As a result, this approach allowed the synthesis of both antipodes of antidepressants fluoxetine, atomoxetine, and nisoxetine [128]. 

This approach was also taken for reduction of 3-oxo-3-phenylpropanenitrile for the synthesis of precursors for both antipodes of fluoxetine, atomoxetine, and nisoxetine, which are popular serotonin/norepinephrine reuptake inhibitors. " Four enzymes were found to reduce this substrate, and by changing the enzyme, both enantiomers of 3-hydroxy-3-phenylpropanitrile could be prepared with a high ee as shown in Scheme 33.1b. 

SCHEME 33.1. Screening of reductase library from baker s yeast expressed in E. coli for reduction of (a) ethyl 2-chloro-3-oxoalkanoates and (b) 3-oxo-3-phenylpropanenitrile. 

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