74562-04-2

Upstream product

• 67-56-1 methanol 
• 532-24-1 tropinone 
• 53955-90-1 (+)-2α-carbomethoxytropinone 
• 532-24-1 tropinone 
• 53955-92-3 (R)-allopseudoecgonine methyl ester 
• 36127-17-0 methyl 8-methyl-3-oxo-8-azabicyclo<3.2.1>octan-2-carboxylate 

Downstream Products

• 43021-26-7 methyl 8-methyl-8-azabicyclo[3.2.1]oct-2-ene-2-carboxylate 
• 372158-01-5 1-[(1R,2S,3S,5S)-2-(tert-Butyl-dimethyl-silanyloxymethyl)-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl]-2-phenyl-ethanone 
• 372158-04-8 (1R,2S,3S,5S)-8-Methyl-3-phenylacetyl-8-aza-bicyclo[3.2.1]octane-2-carboxylic acid 
• 372158-03-7 1-((1R,2S,3S,5S)-2-Hydroxymethyl-8-methyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-ethanone 
• 668-19-9 (-)-Allococaine 

Relevant academic research and scientific papers

The Discovery of an Unusually Selective and Novel Cocaine Analog: Difluoropine. Synthesis and Inhibition of Binding at Cocaine Recognition Sites

Cocaine is a stimulant drug with a high abuse liability. Although it inhibits several monamine transporters in the mammalian brain, its primary mechanism of action has been ascribed to its inhibition of the dopamine transporter. The synthesis, characterization, and receptor binding properties of all eight isomers of a unique tropane analog, 2-carbomethoxy-3-tropane is described. In addition, we report that the S-enantiomer, (S)-(+)-2β-carbomethoxy-3α-tropane, Difluoropine, is a potent (IC50 10.9 nM) and selective (324 ) ligand for the dopamine transporter.

Stereoselective deprotonation of tropinone and reactions of tropinone lithium enolate

Tropinone (6) was deprotonated with lithium diisopropylamide and with chiral lithium amides (18-24) and the resulting enolates (two enantiomers) were treated with electrophiles.The aldol reaction with benzaldehyde and deuteration were both diastereoselective.The former yielded only one isomer (exo, anti) of the aldol 8a; the latter proceeded from the exo face.This selectivity permitted us to probe the deprotonation of tropinone with lithium amides; it was concluded that the reaction involves predominantly the exo axial protons.The reaction of tropinone enolate with ethyl chloroformate led, via a ring opening, to the cycloheptenone derivative 9.The reaction with methyl cyanoformate yielded, in the presence of silver acetate and acetic acid, the β-ketoester 8b; however, in the absence of these additives, and especially when 12-crown-4 was added to the enolate, a ring opening leading to the pyrrolidine derivative 10 occured instead.Deprotonation of tropinone with chiral amides proceeded with modest enantioselectivity.A synthesis of non-racemic anhydroecgonine via this strategy allowed establishing the absolute stereochemistry of deprotonation.