33425-91-1

Upstream product

• 529-20-4 2-methylphenyl aldehyde 
• 98-80-6 phenylboronic acid 
• 341-69-5 orphenadrine hydrochloride 
• 1517-59-5 (R)-o-methylbenzhydrol 
• 107-99-3 2-(dimethylamino)ethyl chloride 
• 1078-58-6 diphenylzinc 
• 4584-46-7 (2-chloroethyl)dimethylamine hydrochloride 
• 1184184-70-0 (R)-N-{2-[(2-bromophenyl)phenylmethoxy]ethyl}-N,N-dimethylamine 
• 74-88-4 methyl iodide 
• 5472-13-9 2-methylbenzhydrol 

Relevant academic research and scientific papers

Enantioseparation and determination of orphenadrine in rat plasma and its application to a stereoselective pharmacokinetic study

A simple, sensitive, and enantioselective HPLC-MS/MS method has been developed for the determination of orphenadrine (ORP) enantiomers in rat plasma for the first time. The method used diphenhydramine as the internal standard (IS), and plasma samples were extracted by liquid-liquid extraction with satisfactory recovery. Chiral separation of the ORP enantiomers was obtained on a Chiralcel OD-RH column (150 mm × 4.6 mm, 5 μm). The mobile phase consists of acetonitrile-ammonium bicarbonate buffer (30 mM, pH 9.0) (80?:?20, v/v). Sufficient resolution (Rs= 3.562) was achieved in a short analysis time (7 min). The multiple reaction monitoring (MRM) mode was used for the detection of ORP enantiomers and IS. The transitions ofm/z270.0 → 181.1 and 256.2 → 167.1 were chosen for monitoring the ORP enantiomers and IS, respectively. Linearity was confirmed in the range of 0.1-50.0 ng mL?1with the lower limit of quantification of 0.1 ng mL?1for both ORP enantiomers in plasma. After validation, the method was applied to the enantioselective pharmacokinetic study of ORP enantiomers in rat plasma following oral administration of 10 mg kg?1racemic ORP. Significant differences (Pmax, AUC,t1/2, CL,Vd, MRT, and VRT, which indicated that enantioselective pharmacokinetic behavior of ORP enantiomers was present in rats.

Binaphthyl-prolinol chiral ligands: Design and their application in enantioselective arylation of aromatic aldehydes

Binaphthyl-prolinol ligands were designed and applied in enantioselective arylation of aromatic aldehydes and sequential arylation-lactonization of methyl 2-formylbenzoate. Under optimized conditions, the reactions provided the desired diarylmethanols and 3-aryl phthalides in up to 96% yields with up to 99% ee and up to 89% yields with up to 99% ee, respectively. In particular, essentially optically pure 3-aryl phthalides (over 99% ee) were obtained in large quantities through recrystallization. This journal is

Chiral Lithium Amido Aryl Zincates: Simple and Efficient Chemo- and Enantio-Selective Aryl Transfer Reagents

An enantioselective aryl transfer is promoted using chiral tricoordinated lithium amido aryl zincates that are easily accessible reagents and whose chiral appendage is simply recovered for reuse. The arylation reaction is run in good yields (60 % average on twenty substrates) and high enantiomeric excesses (95 % ee average). This occurs whatever the ortho, meta, or para substituent borne by the substrate and a complete chemoselectivity is observed with respect to the aldehyde function. Sensitive groups such as nitriles, esters, ketones, and enolisable substrates resist to the action of the ate reagent, warranting a large scope to this methodology.

Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process

A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an 2-arene:2-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.

CuII-catalyzed asymmetric hydrosilylation of diaryl- and aryl heteroaryl ketones: Application in the enantioselective synthesis of orphenadrine and neobenodine

With certain amounts of sodium tert-butoxide and tert-butanol as additives, catalytic amounts of an inexpensive and easy-to-handle copper source Cu(OAc)2·H2O, a commercially available and air-stable non-racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine. Copyright

The first asymmetric halogen/metal-exchange reaction: Desymmetrization of alcohols with enantiotopic bromoarene substituents

Desymmetrizations of the prochiral bis(bromoaryl)alcohols 1 and 4 were effected by treatment with iPr2Mg and enantiomerically pure lithium alkoxides. The resulting arylmagnesium compounds were quenched with various electrophiles. The absolute and (if relevant) relative configurations of the resulting products were determined. The best ee/yield combination was obtained for the protonolysis furnishing monobromoalcohol (R)-2 (53% ee, 51% yield). The latter was converted into (R)-orphenadrine, an antihistaminic and anticholinergic drug.

Development of asymmetric nickel-catalyzed arylation of aromatic aldehydes with arylboron reagents

The development of the nickel-catalyzed 1,2-addition of triarylboroxins to aromatic aldehydes in the presence of a phosphine ligand is described. This development allowed the asymmetric nickel-catalyzed 1,2-addition of arylboron reagents to aromatic aldehydes. The enantioselectivity is synthetically acceptable (up to 81 % ee) using 1-naphthaldehyde and 2-substituted aromatic aldehydes as substrates. The results have enantioselectivity comparable to the best results reported by us for the rhodium-catalyzed arylation of aromatic aldehydes. Georg Thieme Verlag Stuttgart · New York.