88762-93-0

Upstream product

• 90-85-7 (+/-)-erythro-2-(methyl-benzyl-amino)-1-phenyl-propanol-⁽¹⁾ 
• 100-44-7 benzyl chloride 
• 24221-86-1 (+)-(1S,2R)-ephedrine hydrochloride 
• 299-42-3 ephedrine 
• 61347-76-0 NH-benzyl-(1R,2S)-norephedrine 
• 77-78-1 dimethyl sulfate 
• 100-39-0 benzyl bromide 
• 258827-43-9 (2rac,4S,5R)-3,4-dimethyl-2,5-diphenyl-1,3-oxazolidine 
• 16735-30-1 2-(N-benzyl-N-methylamino)-1-phenylpropan-1-one 
• 90-81-3 ephedrine 
• 90-82-4 rac-pseudoephedrine 
• 100-52-7 benzaldehyde 
• 50-00-0 formaldehyd 
• 64-18-6 formic acid 

Downstream Products

• 774596-70-2 (3S,4R)-N⁽²⁾,3-dimethyl-4-phenyl-1,2,3,4-tetrahydroisoquinoline 
• 1255530-21-2 C₂₁H₂₅NO₂ 
• 159099-80-6 (1S,2S)-2-(N-benzyl-N-methylamino)-1-phenyl-1-propanol 
• 90-85-7 (1R,2S)-1-phenyl-2-(N-methyl-N-benzylamino)propan-1-ol 
• 573701-36-7 2-Diazo-3-oxo-butyric acid (1R,2S)-2-(benzyl-methyl-amino)-1-phenyl-propyl ester 

Relevant academic research and scientific papers

A dimethylzinc/diphenylphosphinoylimine approach to the asymmetric synthesis of the calcimimetic agent NPS R-568

An asymmetric synthesis of the calcimimetic agent NPS R-568 using a (1R,2S)-N-benzylephedrine-promoted addition of dimethylzinc to a diphenylphosphinoylimine derived from 3-methoxybenzaldehyde is described. The enantiomeric ratio of the key amine fragment was determined to be 93:7 (86% ee), favoring the (R)-enantiomer by derivatization and chiral stationary phase HPLC analysis.

A stereo-controlled synthesis of 2,4-dimethyl-4-hydroxy-16- phenylhexadecanoic acid 1,4-lactone and its PPAR activities

A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16- phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural product libraries. The synthesis of 1 was accomplished starting from vinylmethyl ketone. Ring formation of the α,γ dialkyl γ-lactone was achieved via the stereo-controlled reaction of a ketyl radical anion with a chiral methacrylate. In the PPAR agonistic assay, the most potent of the four stereoisomers had EC50 values of 12 μM for mPPARα, 9 μM for mPPARδ and >100 μM for mPPARγ.

Enantiospecific Stereodivergent Synthesis of trans- and cis-N(2), 3-Dimethyl- 4-phenyl-1, 2, 3, 4-tetrahydroisoquinolines

The acid-promoted cyclizations of a range of N-benzylethanolamines (derived from pseudoephedrine or ephedrine) give the corresponding trans-N(2), 3-dimethyl-4-phenyl-1, 2, 3, 4- tetrahydroisoquinolines with high levels of diastereoselectivity and in good yields of isolated product. The cyclizations of the corresponding chromium tricarbonyl complexes are rendered completely stereoselective. Acidpromoted cyclization of N-(3′, 4′- dimethoxybenzyl) ephedrine and its chromium tricarbonyl complex occur with complementary diastereoselectivities to give trans- and cis-N(2), 3-dimethyl-4- phenyl-6, 7-dimethoxy-1, 2, 3, 4-tetrahydro- isoquinoline, respectively, in >99:1 d.r. The latter is consistent with a "double inversion" mechanism, which involves neighboring group participation by the chromium tricarbonyl moiety followed by rearomatization to give the corresponding cis-tetrahydroisoquinoline with overall retention of configuration.

N-Pyridylmethylephedrine derivatives in the catalytic asymmetric addition of diethylzinc to aldehydes and diphenylphosphinoylimines

N-Pyridylmethyl-substituted Ephedra derivatives were synthesized by either direct alkylation or reductive alkylation of (1R,2S)-norephedrine, (1S,2S)-pseudo norephedrine, and (1R,2S)-ephedrine. These derivatives were then employed in asymmetric addition reactions with diethylzinc and aldehydes and diphenylphosphinoylimines. The use of the diastereomers from the Ephedra family allowed for a systematic evaluation of the contribution of the N-pyridylmethyl.

Enantioselective diethylzinc addition to the exocyclic C{double bond, long}N double bond of some 4-arylideneamino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-one derivatives

4-Arylideneamino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 2a-f have been evaluated as substrates in the enantioselective diethylzinc addition reaction in the presence of (1S,2R)-N-alkyl-N-benzylnorephedrines 3a-d as chiral ligands. The utility of using a dual catalytic system (amino alcohol/halosilane) for the diethylzinc addition reaction has been also examined. The addition products 4-(1-arylpropyl)amino-3-mercapto-6-methyl-4H-1,2,4-triazin-5-ones 4a-f were obtained in high yields and with enantiomeric excesses of up to 92%. The treatment of arylimines 2a-f with a diethylzinc reagent did not affect the hetero-ring opening although the C{double bond, long}N double bond of the lateral chain did undergo an addition reaction to yield the C-ethylated products 4a-f. The reductive cleavage of the 1,2,4-triazinyl heterocyclic ring from addition products 4a-f led smoothly to the corresponding free primary amines 5a-f without a significant loss of enantiomeric purity.

Development of a solid-phase 'asymmetric resin-capture-release' process: Application of an ephedrine chiral resin in an approach to γ- butyrolactonest

The potential of a solid-phase asymmetric resin-capture-release strategy for high-throughput synthesis has been evaluated. Fukuzawa's Sm(II)-mediated, asymmetric approach to γ-butyrolactones was selected to illustrate the feasibility of such a process. α,β-Unsaturated esters immobilised on an ephedrine chiral resin have been applied in an asymmetric approach to γ-butyrolactones. Lactone products are obtained in moderate isolated yields with selectivities up to 96% ee. In addition, we have shown that the ephedrine resin can be conveniently recovered and recycled although in some cases lower yields were obtained on reuse of the chiral resin. A short synthesis of a moderate DNA-binding microbial metabolite using asymmetric resin-capture-release is also described.

Diastereoselectivity in the reduction of α-oxy- and α-amino-substituted acyclic ketones by polymethylhydrosiloxane

Diastereoselectivity in the reduction of α-alkoxy-, α-acyloxy-, and α-alkylamino-substituted ketones with polymethylhydrosiloxane (PMHS) in the presence of fluoride ion catalysis was investigated. High syn-selectivity was observed in the reduction of α-alkoxy, α-acyloxy, and α-dialkylamino ketones. Reduction of α-monoalkylamino ketone proceeded in anti-selective manner with moderate selectivity. The observed selectivity is explained based on Felkin-Anh and Cram-chelate models.

Stereoselective formation and rearrangement of morpholinium ylides derived from copper carbenoids

Amino diazoacetoacetates 4a-e and 7a,b were prepared from readily available amino alcohols and subjected to copper-catalyzed carbene-transfer reaction. Substrates 4c-e furnished the morpholin-2-ones 5c-e in good yield via the corresponding cyclic ammonium ylides, albeit with poor diastereoselectivity. Substrates 4a,b failed to provide the corresponding morpholinones, perhaps as a result of steric congestion. Cyclic substrates 7a,b underwent conversion to bicyclic morpholinones 8 and 9 in good yield and with moderate to good diastereoselectivity. This result is rationalized via control of the transiently stereogenic ammonium center of the intermediate bicyclic ylides.

Synthesis of N-(dialkylaminoalkyl)alcohols by homogeneously catalyzed hydrogenolysis of cyclic N,O-acetals

The homogeneously catalyzed hydrogenation of 1,3-oxazolidines affording unsymmetrically substituted 2-N-(dialkylamino)ethanols is reported showing for the first time that Rh(I) catalysts based on chelating diphosphines can be advantageous for this reaction.

The Reductive Cleavage of Cyclic Aminol Ethers to N,N-Dialkylamino-derivatives: Modifications to the Eschweiler-Clarke Procedure

The reductive cleavage of cyclic aminol ethers to give N-alkylamino-derivatives in very high yields can be achieved using chlorotrimethylsilane in the presence of sodium cyanoborohydride: in the case of cyclic aminol ethers derived from formaldehyde the Eschweiler-Clarke reaction can be carried out in formic acid heated under reflux in the absence of formaldehyde.