36794-52-2

Usage

InChI:InChI=1/C19H23N.C4H4O4/c1-4-10-17(11-5-1)16-19(18-12-6-2-7-13-18)20-14-8-3-9-15-20;5-3(6)1-2-4(7)8/h1-2,4-7,10-13,19H,3,8-9,14-16H2;1-2H,(H,5,6)(H,7,8)/b;2-1-

Synthetic route

N-benzoylpiperidine (776-75-0) + benzylmagnesium chloride (6921-34-2) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Stage #1: N-benzoylpiperidine With bis(triphenylphosphine)carbonyliridium(I) chloride; 1,1,3,3-Tetramethyldisiloxane In dichloromethane at 20℃; for 0.333333h; Stage #2: benzylmagnesium chloride at -78 - 20℃; for 4h; chemoselective reaction;	95%

piperidine (110-89-4) + benzyl bromide (100-39-0) + benzaldehyde (100-52-7) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Stage #1: piperidine; benzyl bromide; benzaldehyde With trifluoroacetic acid; zinc In acetonitrile for 1.5h; Mannich type reaction; Inert atmosphere; Stage #2: With ammonium chloride In water; acetonitrile	77%

1,1'-benzylidenedipiperidine (2538-76-3) + benzyl bromide (100-39-0) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
With chloro-trimethyl-silane; diisopropylamine; zinc In benzene at 20℃; for 6h;	46%

1-(butoxyphenylmethyl)piperidine (5351-11-1) + phenylmagnesium bromide (1589-82-8) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
With diethyl ether

benzylmagnesium chloride (6921-34-2) + α-piperidino-phenylacetic acid nitrile → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

piperidine (110-89-4) + benzyl(bromo)zinc (62673-31-8) + benzaldehyde (100-52-7) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
In acetonitrile at 20℃; for 3h;

piperidine (110-89-4) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: mercury (II)-chloride; calcium sulfate 2: diethyl ether View Scheme
Multi-step reaction with 3 steps 1: benzene / Unter Entfernen des entstehenden Wassers. 2: potassium carbonate 3: diethyl ether View Scheme

1,1'-benzylidenedipiperidine (2538-76-3) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate 2: diethyl ether View Scheme

benzaldehyde (100-52-7) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: mercury (II)-chloride; calcium sulfate 2: diethyl ether View Scheme

1,5-dibromo-pentane (111-24-0) + (R,S)-1,2-diphenylethylamine (25611-78-3) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
With potassium carbonate In acetonitrile at 20℃; for 72h; Inert atmosphere;

piperidine (110-89-4) + diphenyl acetylene (501-65-5) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Mor-DaIPhos-AuCl; silver tetrakis(pentafluorophenyl)borate / toluene / 16 h / 110 °C / Inert atmosphere; Sealed cap 2: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 20 °C View Scheme

(E)-1-(1,2-diphenylvinyl)piperidine → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 20℃;	167 mg

cis-Stilbenyl-diisobutyl-aluminium (20259-38-5, 26076-78-8) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: copper(l) chloride / tetrahydrofuran / 0.5 h / 22 °C / Inert atmosphere 2: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 12 h / 22 °C / Inert atmosphere View Scheme

diphenyl acetylene (501-65-5) → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
Multi-step reaction with 3 steps 1: bis(triphenylphosphine)nickel(II) chloride / hexane / 12 h / 60 °C / Inert atmosphere 2: copper(l) chloride / tetrahydrofuran / 0.5 h / 22 °C / Inert atmosphere 3: sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 12 h / 22 °C / Inert atmosphere View Scheme

C19H21N → (±)-1-(1,2-diphenylethyl)piperidine (36794-52-2)

Conditions	Yield
With sodium tris(acetoxy)borohydride; acetic acid In dichloromethane at 22℃; for 12h; Inert atmosphere;	63.5 mg

(±)-1-(1,2-diphenylethyl)piperidine (36794-52-2) → (+/-)-1-(1,2-diphenylethyl)piperidine hydrochloride (28383-15-5)

Conditions	Yield
With hydrogenchloride; water at 4 - 40℃;

(±)-1-(1,2-diphenylethyl)piperidine (36794-52-2) → (+)-diphenidine + (-)-diphenidine

Conditions	Yield
With carboxymethyl-β-cyclodextrin (degree of substitution: 0.5) In aq. phosphate buffer at 25℃; pH=2.5; Reagent/catalyst; Resolution of racemate;

Upstream product

• 5351-11-1 1-(butoxyphenylmethyl)piperidine 
• 1589-82-8 phenylmagnesium bromide 
• 6921-34-2 benzylmagnesium chloride 
• 110-89-4 piperidine 
• 62673-31-8 benzyl(bromo)zinc 
• 100-52-7 benzaldehyde 
• 2538-76-3 1,1'-benzylidenedipiperidine 
• 100-39-0 benzyl bromide 
• 501-65-5 diphenyl acetylene 
• 776-75-0 N-benzoylpiperidine 
• 20259-38-5 cis-Stilbenyl-diisobutyl-aluminium 
• 111-24-0 1,5-dibromo-pentane 
• 25611-78-3 (R,S)-1,2-diphenylethylamine 

Downstream Products

• 28383-15-5 (+/-)-1-(1,2-diphenylethyl)piperidine hydrochloride 

Relevant academic research and scientific papers

Tertiary amine synthesis: Via reductive coupling of amides with Grignard reagents

A new iridium catalyzed reductive coupling reaction of Grignard reagents and tertiary amides affording functionalised tertiary amine products via an efficient and technically-simple one-pot, two-stage experimental protocol, is reported. The reaction-which can be carried out on gram-scale using as little as 1 mol% Vaska's complex [IrCl(CO)(PPh3)2] and TMDS as the terminal reductant for the initial reductive activation step-tolerates a broad range of tertiary amides from (hetero)aromatic to aliphatic (branched, unbranched and formyl) and a wide variety of alkyl (linear, branched), vinyl, alkynyl and (hetero)aryl Grignard reagents. The new methodology has been applied directly to bioactive molecule synthesis and the high chemoselectivity of the reductive coupling of amide has been exploited in late stage functionalization of drug molecules. This reductive functionalisation of tertiary amides provides a new and practical solution to tertiary amine synthesis.

Cu-Catalyzed electrophilic amination of internal alkynes via hydroalumination

A straightforward and efficient method for the synthesis of 1,2-diaryl-substituted enamines through the Cu-catalyzed electrophilic amination reaction of O-benzoyl hydroxylamines with vinylaluminum reagents generated in situ from the Ni-catalyzed hydroalumination of readily accessible internal aryl acetylenes is described. The amination is catalyzed by 1 mol% CuCl without any additive at ambient temperature to afford new versatile enamines in good yield (61-91%) with high selectivity (>98% E-enamine).

Stereo- and regioselective gold-catalyzed hydroamination of internal alkynes with dialkylamines

We report the use of a P,N-ligand to support a gold complex as a state-of-the-art precatalyst for the stereoselective hydroamination of internal aryl alkynes with dialkylamines to afford E-enamine products. Substrates featuring a diverse range of functional groups on both the amine (ether, sulfide, N-Boc amine, fluoro, nitrile, nitro, alcohol, N-heterocycles, amide, ester, and carboxylic acid) and alkyne (ether, N-heterocycles, N-phthalimide amines, and silyl ethers) are accommodated with synthetically useful regioselectivity.

Three-component synthesis of α-branched amines under barbier-like conditions

(Chemical Equation Presented) An array of α-branched amines has been prepared by using an expedient three-component Mannich-type reaction among organic halides, aldehyde derivatives, and amines. The experimental procedure, which is characterized by its simplicity, employs zinc dust for the in situ generation of organozinc reagents. We show that this Barbier-like protocol constitutes a useful entry to diarylmethylamines, 1,2-diarylethylamines, α- or β-amino esters, benzylamines, and β-arylethylamines.

NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds

We resolved 1,2-diphenylethylamine (DPEA) into its (S)- and (R)-enantiomer and used them as precursors for synthesis of (S)- and (R)-1-(1,2-diphenylethyl)piperidine, flexible homeomorphs of the NMDA channel blocker MK-801. We also describe the synthesis o

Zinc-mediated allylation and alkylation of aminals in the presence of TMSCl and diisopropylamine

(Chemical Equation Presented) An alkylation of aminals with organozinc reagents derived from allyl bromide, benzyl bromide, α-bromoacetate, and α-bromonitrile proceeded efficiently in the presence of TMSCl and diisopropylamine. This reaction system was applied to the synthesis of an antispasmodic: butaverine.

One-step three-component coupling of aromatic organozinc reagents, secondary amines, and aromatic aldehydes into functionalized diarylmethylamines

Numerous functionalized diarylmethylamines have been synthesized in high yield according to a one-step three-component coupling between an aromatic organozinc reagent, a secondary amine, and an aromatic aldehyde. Both organozinc species and aldehyde can bear a functional group and either aromatic or non-aromatic amines can be used in this versatile procedure.

1,2-diarylethylamines for treatment of neurotoxic injury

Compounds, compositions and methods of treatment are described to control brain damage associated with anoxia or ischemia which typically follows stroke, cardiac arrest or perinatal asphyxia. The treatment includes administration of a 1,2-diarylethylamine compound as an antagonist to inhibit excitotoxic actions at major neuronal excitatory amino acid receptor sites. Compounds of interest are those of the formula wherein each of R1 and R2 is a group independently selected from hydrido, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, hydroxyl, alkoxy, halo, cyano, nitro and mercapto, or wherein R1 and R2 may be taken together to form an oxo group or to form a saturated or partially unsaturated carbocyclic group having three to eight ring carbons; wherein each of Ar1 and Ar2 is a group independently selected from aryl and heteroaryl having one or two heteroatoms selected from N, O and S; and wherein any of the foregoing Ar1 and Ar2 groups having a substitutable position msy be substituted with one or more radicals selected from hydrido, alkyl, cycloalkyl, halo, haloalkyl, alkenyl, alkynyl, hydroxyl, hydroxyalkyl, alkoxy, alkoxyalkyl, amino, cyano, nitro and mercapto; wherein X is selected from CH, CH2, NH, O and S, to form a ring having five to eight members provided that such ring is saturated or contains one double bond or is benzo-fused; and wherein Y is one or more a groups selected from hydrido, alkyl, cycloalkyl, halo, haloalkyl, alkenyl, alkynyl, hydroxyl, hydroxy-alkyl, alkoxy, alkoxyalkyl, amino, cyano, nitro and mercapto; or a pharmaceutically acceptable salt thereof.