345349-97-5

Upstream product

• 96847-52-8 (1R,2S)-2-oxo-1-phenyl-3-oxabicyclo[3.1.0]hexane 
• 98-80-6 phenylboronic acid 
• 692730-97-5 (Z)-4-(tert-butyldimethylsiloxy)-3-phenylbut-2-en-1-ol 
• 910028-42-1 (1R,2S)-2-Hydroxymethyl-1-phenyl-cyclopropanecarbonitrile 
• 140-29-4 phenylacetonitrile 
• 172016-06-7 (1R,2S)-1-phenyl-2-(hydroxymethyl)-N,N-diethylcyclopropanecarboxamide 

Downstream Products

• 101152-94-7 (1R,2S)-cis-milnacipran hydrochloride 
• 101152-94-7 (1S,2R)-milnacipran hydrochloride 
• 96847-54-0 (1R,2S)-milnacipran 

Relevant academic research and scientific papers

Asymmetric syntheses of pharmaceuticals containing a cyclopropane moiety using catalytic asymmetric Simmons-Smith reactions of allylalcohols: Syntheses of optically active tranylcypromine and milnacipran

Asymmetric synthesis of tranylcypromine was achieved using an enantioselective Simmons-Smith cyclopropanation catalyzed by a simple disulfonamide derived from an -amino acid. The optically active milnacipran was also synthesized by porcine pancreas lipase-catalyzed selective monoacylation of the C4-hydroxy group in (Z)-2-phenylbut-2-ene-1,4-diol and the enantioselective Simmons-Smith cyclopropanation as the key steps.

Synthesis of enantiomerically pure milnacipran analogs and inhibition of dopamine, serotonin, and norepinephrine transporters

A series of Milnacipran analogs with variation in the aromatic moiety were prepared in high enantiomeric excess. Structure-activity relationships for two parallel enantiomeric series are described. The (-)-(1R,2S)-naphthyl analog (8h) showed the highest potency in the two series and is a triple reuptake inhibitor of the SERT, NET, and DAT.

Synthesis of (+)- and (-)-milnaciprans and their conformationally restricted analogs

Reaction of (R)-epichlorohydrin [(R)-5] and phenylacetonitrile (6) in the presence of NaNH2 in benzene gave a cyclopropane derivative which was isolated as lactone 4 [(1S,2R)-2-oxo-1-phenyl-3-oxabicyclo[3,1,0]hexane] of 96% e.e. in 67% yield, after alkaline hydrolysis of the cyano group. Compound 4 was readily converted to (+)-milnacipran [(+)-1], by which the absolute stereochemistry of (+)-1 was confirmed. (1S,2R)-1-phenyl-2-[(S)-1-aminoethyl]-cyclopropane-N,N-diethylcarboxam ides (2), a conformationally restricted analog of 1, was also synthesized in high enantiomeric purity from 4. Starting from (S)-epichlorohydrin [(S)-5], their corresponding enantiomers, namely (-)-milnacipran [(-)-1] and ent-2, were also synthesized.