13002-65-8

Basic information

• Product Name: 2-[4-[(E)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine
• Synonyms: 2-[4-[(E)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine;CIS-TAMOXIFEN;(E)-1,2-Diphenyl-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-butene;(E)-α-[4-[2-(Dimethylamino)ethoxy]phenyl]-β-ethylstilbene;2-[4-[(E)-1,2-Diphenyl-1-butenyl]phenoxy]-N,N-dimethylethaneamine;N,N-Dimethyl-2-[4-[(E)-1,2-diphenyl-1-butenyl]phenoxy]ethanamine;N,N-Dimethyl-2-[p-[(E)-1,2-diphenyl-1-butenyl]phenoxy]ethanamine;(E)-TaMoxifen
• CAS NO: 13002-65-8
• Molecular Formula: C₂₆H₂₉NO
• Molecular Weight: 371.56
• Product Categories: Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Protein Kinase Inhibitors and Activators
• Mol File: 13002-65-8.mol
• Article Data: 29

Chemical Properties

• Melting Point: 72-74° from methanol
• Boiling Point: 501.18°C (rough estimate)
• Appearance: /
• Density: 1.0630 (rough estimate)
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: Amber Vial, -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)
• Stability: Light Sensitive
• CAS DataBase Reference: 2-[4-[(E)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-[4-[(E)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine(13002-65-8)
• EPA Substance Registry System: 2-[4-[(E)-1,2-diphenylbut-1-enyl]phenoxy]-N,N-dimethyl-ethanamine(13002-65-8)

Safety Data

• Hazardous Substances Data: 13002-65-8(Hazardous Substances Data)

Usage

Chemical Properties

White to Off-White Solid

Uses

Different sources of media describe the Uses of 13002-65-8 differently. You can refer to the following data:
1. (E)-Tamoxifen is an antineoplastic.
2. Antineoplastic.

InChI:InChI=1/C28H32/c1-4-27(24-14-7-5-8-15-24)28(25-16-9-6-10-17-25)26-20-18-23(19-21-26)13-11-12-22(2)3/h5-10,14-22H,4,11-13H2,1-3H3/b28-27+

Synthetic route

ICI 77949 (69967-79-9) + (2-chloroethyl)dimethylamine hydrochloride (4584-46-7) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
With potassium carbonate In ethanol; toluene at 80 - 85℃; for 3h; Inert atmosphere;	97%
With sodium ethanolate In ethanol for 24h; Heating;	62%
With sodium hydride 1.) DMF, 2.) 60 deg C, 30 min; Yield given. Multistep reaction;

[2-(4-iodophenoxy)ethyl]dimethylamine (93790-54-6) + (Z)-2-(1,2-diphenylbut-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (624731-39-1) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
With sodium hydroxide; bis(tri-t-butylphosphine)palladium(0) In tetrahydrofuran at 60℃; for 24h; Suzuki-Miyaura coupling;	95%
With sodium hydroxide; bis(tri-t-butylphosphine)palladium(0) In tetrahydrofuran at 60℃; for 24h; Suzuki-Miyaura coupling;	95%

iodobenzene (591-50-4) + (Z)-1-(4',4',5',5'-tetramethyl-1',3',2'-dioxaborolan-2'-yl)-1-[4''-(2'''-dimethylaminoethoxy)phenyl]-2-phenyl-1-butene (865999-31-1) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
With sodium hydroxide; bis(tri-t-butylphosphine)palladium(0) In tetrahydrofuran at 60℃; for 24h;	75%

(E)-1,2-diphenylbut-1-en-1-yl dimethylcarbamate + (4-(2-(dimethylamino)ethoxy)phenyl)magnesium bromide (35258-27-6) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
With N,N'-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene hydrochloride; palladium diacetate In tetrahydrofuran at 50℃; for 18h; Schlenk technique; Inert atmosphere; Sealed tube; stereoselective reaction;	70%

(E)-1,2-diphenyl-1-butene boronic acid (918793-63-2) + [2-(4-bromophenoxy)ethyl]dimethylamine (2474-07-9) → 1,2-diphenyl-butan-1-one (16282-16-9) + tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In 1,2-dimethoxyethane; water Suzuki-Miyaura cross-coupling; Heating;	A n/a B 65% C n/a

N,N-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethanamine (873078-93-4) + (2R,3R)-2-ethyl-2,3-diphenyloxirane → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Stage #1: (2R,3R)-2-ethyl-2,3-diphenyloxirane With N,N,N,N,-tetramethylethylenediamine; tert.-butyl lithium In diethyl ether; pentane at -78℃; for 0.25h; Stage #2: N,N-dimethyl-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy)ethanamine In diethyl ether at 20 - 38℃;	63%

2-(dimethylamino)ethyl chloride (107-99-3) + (E,Z)-4-(1,2-diphenylbut-1-en-1-yl)phenol (68684-63-9) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
In N,N-dimethyl-formamide at 50℃; for 0.5h;	A 51% B 44%
With sodium hydride In N,N-dimethyl-formamide at 50℃; for 0.5h;

4-(4-[2-dimethylaminoethoxy]phenyl)-3,4-diphenylbut-1-ene → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
With potassium tert-butylate In dimethyl sulfoxide at 20℃; for 1h;	A 39% B 37%

(1-phenylpropyl)phosphonic acid di-o-tolyl ester (872254-52-9) + (4-(2-(dimethylamino)ethoxy)phenyl)(phenyl)methanone (51777-15-2) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
Stage #1: (1-phenylpropyl)phosphonic acid di-o-tolyl ester With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: (4-(2-(dimethylamino)ethoxy)phenyl)(phenyl)methanone In tetrahydrofuran; hexane at -78℃; for 48h; Horner reaction;	A 28% B 12%

tamoxifen (10540-29-1) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
With hydrogenchloride In ethanol for 4h; Heating;

ICI 77949 (69967-79-9) + (2-chloroethyl)dimethylamine hydrochloride (4584-46-7) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
With sodium methylate; hydrogen cation Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

(1S,2R)-1-[4-(2-Dimethylamino-ethoxy)-phenyl]-1,2-diphenyl-butan-1-ol (748-97-0, 77542-06-4, 77542-07-5, 81992-83-8, 111914-74-0) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
With hydrogenchloride In ethanol for 0.333333h; Heating; Yield given;

[2-(4-bromophenoxy)ethyl]dimethylamine (2474-07-9) + triethylaluminum (97-93-8) + diphenyl acetylene (501-65-5) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) 1.) hexane, toluene, 90 deg C, 24 h, 2.) THF, reflux, 24 h; Yield given. Multistep reaction;

1-phenyl-1-butyne (622-76-4) + [2-(4-iodophenoxy)ethyl]dimethylamine (93790-54-6) + p-I-C6H4-Si(Me2)CH2CH2CONH-resin → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8) + {2-[4-(1-Benzhydrylidene-propyl)-phenoxy]-ethyl}-dimethyl-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydroxide; 3,5-dimethoxyphenol; tetrakis(triphenylphosphine)platinum; trifluoroacetic acid; bis(pinacol)diborane 1.) DMF, 80 deg C, 2.) DME, 25 deg C, 18 h, 3.) 25 deg C, 18 h, 4.) CH2Cl2; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

1-phenyl-1-butyne (622-76-4) + 4-tolyl iodide (624-31-7) + p-I-C6H4-Si(Me2)CH2CH2CONH-resin → (E)-tamoxifen (13002-65-8) + (Z)-(1-(p-tolyl)but-1-ene-1,2-diyl)dibenzene (116454-42-3) + {2-[4-(1-Benzhydrylidene-propyl)-phenoxy]-ethyl}-dimethyl-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydroxide; 3,5-dimethoxyphenol; tetrakis(triphenylphosphine)platinum; trifluoroacetic acid; bis(pinacol)diborane 1.) DMF, 80 deg C, 2.) DME, 25 deg C, 18 h, 3.) 25 deg C, 18 h, 4.) CH2Cl2, 10 min; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

1-phenyl-1-butyne (622-76-4) + 4-tolyl iodide (624-31-7) + p-I-C6H4-Si(Me2)CH2CH2CONH-resin → (E)-tamoxifen (13002-65-8) + C23H21I + {2-[4-(1-Benzhydrylidene-propyl)-phenoxy]-ethyl}-dimethyl-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium hydroxide; 3,5-dimethoxyphenol; tetrakis(triphenylphosphine)platinum; Iodine monochloride; bis(pinacol)diborane 1.) DMF, 80 deg C, 2.) DME, 25 deg C, 18 h, 3.) 25 deg C, 18 h, 4.) CH2Cl2, 30 min; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

iodobenzene (591-50-4) + Z-(Et)(C6H5)CC(4-Me2NCH2CH2OC6H4)(B(pin)) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8) + Dimethyl-{2-[4-((Z)-2-phenyl-but-1-enyl)-phenoxy]-ethyl}-amine

Conditions	Yield
With sodium hydroxide; bis(tri-t-butylphosphine)palladium(0) In tetrahydrofuran at 60℃; for 24h; Product distribution; Further Variations:; Reagents; Suzuki-Miyaura coupling;

(2-chloroethyl)dimethylamine hydrochloride (4584-46-7) + (E,Z)-4-(1,2-diphenylbut-1-en-1-yl)phenol (68684-63-9) → tamoxifen (10540-29-1) + (E)-tamoxifen (13002-65-8)

Conditions	Yield
With sodium ethanolate In ethanol for 24h; Heating; Title compound not separated from byproducts;
Stage #1: 1-(4-hydroxyphenyl)-1,2-diphenylbut-1-ene With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; Stage #2: (2-chloroethyl)dimethylamine hydrochloride With potassium iodide In tetrahydrofuran; mineral oil for 12h; Reflux; Overall yield = 80 %; Overall yield = 148.5 mg; Optical yield = 8.108 %de;

diphenyl acetylene (501-65-5) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: tetrahydrofuran; dibutyl ether / 2 h / -10 °C 1.2: 51 percent / triisopropyl borate / tetrahydrofuran; dibutyl ether / -78 - 20 °C 2.1: sodium carbonate / Pd(PPh3)4 / 1,2-dimethoxy-ethane; H2O / Heating View Scheme

(1-(4-methoxyphenyl)but-1-ene-1,2-diyl)dibenzene (69967-78-8) + ethanolic KOH → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: BBr3 / CH2Cl2 / 5 h / -60 - 20 °C 2: EtONa / ethanol / 24 h / Heating View Scheme

1-((Z)-1,2-Diphenyl-buta-1,3-dienyl)-4-methoxy-benzene (857085-82-6) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: aq. H2O2; N2H4*H2O / ethanol; CH2Cl2 / -60 - 20 °C 2: BBr3 / CH2Cl2 / 5 h / -60 - 20 °C 3: EtONa / ethanol / 24 h / Heating View Scheme

1,1-bis(4',4',5',5'-tetramethyl-1',3',2'-dioxaborolan-2'-yl)-2-phenyl-1-butene (865999-18-4) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 55 percent / Pd2(dba)3; P(t-Bu)3; aq. KOH / tetrahydrofuran / 5 h / 20 °C 2: 75 percent / Pd[P(t-Bu)3]2; aq. NaOH / tetrahydrofuran / 24 h / 60 °C View Scheme

[2-(4-iodophenoxy)ethyl]dimethylamine (93790-54-6) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 55 percent / Pd2(dba)3; P(t-Bu)3; aq. KOH / tetrahydrofuran / 5 h / 20 °C 2: 75 percent / Pd[P(t-Bu)3]2; aq. NaOH / tetrahydrofuran / 24 h / 60 °C View Scheme

1-Phenyl-1-propanol (93-54-9) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 95 percent / PBr3 / CH2Cl2 / 20 °C 2.1: 120 h / 130 °C 2.2: 45 percent / NaOH / H2O / 20 °C 3.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 3.2: 12 percent / tetrahydrofuran; hexane / 48 h / -78 °C View Scheme

1-bromopropylbenzene (2114-36-5, 101308-38-7) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 120 h / 130 °C 1.2: 45 percent / NaOH / H2O / 20 °C 2.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: 12 percent / tetrahydrofuran; hexane / 48 h / -78 °C View Scheme

4-Hydroxybenzophenone (1137-42-4) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: 90 percent / sodium ethoxide / ethanol / 24 h / Heating 2.1: n-butyllithium / tetrahydrofuran; hexane / 1 h / -78 °C 2.2: 12 percent / tetrahydrofuran; hexane / 48 h / -78 °C View Scheme

iodobenzene (591-50-4) + 4-CF3C6H4COCr(CO)5(1-)NMe4(1+) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 52 percent / diethyl ether; tetrahydrofuran / 16 h / 20 °C 2.1: BCl3 / CH2Cl2 / 5 h / -41 °C 2.2: 82 percent / Et3N / CH2Cl2 / 14 h / 20 °C 3.1: 95 percent / aq. NaOH / Pd[P(t-Bu)3]2 / tetrahydrofuran / 24 h / 60 °C View Scheme

C17H20MgNSi → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: 52 percent / diethyl ether; tetrahydrofuran / 16 h / 20 °C 2.1: BCl3 / CH2Cl2 / 5 h / -41 °C 2.2: 82 percent / Et3N / CH2Cl2 / 14 h / 20 °C 3.1: 95 percent / aq. NaOH / Pd[P(t-Bu)3]2 / tetrahydrofuran / 24 h / 60 °C View Scheme

E-(Et)(C6H5)CC(C6H5)(SiMe2C5H4N) (624731-31-3) → (E)-tamoxifen (13002-65-8)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: BCl3 / CH2Cl2 / 5 h / -41 °C 1.2: 82 percent / Et3N / CH2Cl2 / 14 h / 20 °C 2.1: 95 percent / aq. NaOH / Pd[P(t-Bu)3]2 / tetrahydrofuran / 24 h / 60 °C View Scheme

(E)-tamoxifen (13002-65-8) → rel-(1R,2S)-1-<4-<2-(dimethylamino)ethoxy>phenyl>-1,2-diphenylbutane (109640-21-3)

Conditions	Yield
With ammonium formate; palladium on activated charcoal In ethanol at 80℃; for 4.5h;	83%

(E)-tamoxifen (13002-65-8) → tamoxifen (10540-29-1)

Conditions	Yield
With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 3h;	51%
With trifluorormethanesulfonic acid In dichloromethane at 0℃; for 3h;	51%
With pyridine; bromine In diethyl ether; dichloromethane for 2h; Ambient temperature; Irradiation; Yield given;

Upstream product

• 10540-29-1 tamoxifen 
• 2474-07-9 [2-(4-bromophenoxy)ethyl]dimethylamine 
• 97-93-8 triethylaluminum 
• 501-65-5 diphenyl acetylene 
• 622-76-4 1-phenyl-1-butyne 
• 93790-54-6 [2-(4-iodophenoxy)ethyl]dimethylamine 
• 624-31-7 4-tolyl iodide 
• 591-50-4 iodobenzene 
• 865999-31-1 (Z)-1-(4',4',5',5'-tetramethyl-1',3',2'-dioxaborolan-2'-yl)-1-[4''-(2'''-dimethylaminoethoxy)phenyl]-2-phenyl-1-butene 
• 872254-52-9 (1-phenylpropyl)phosphonic acid di-o-tolyl ester 
• 51777-15-2 (4-(2-(dimethylamino)ethoxy)phenyl)(phenyl)methanone 
• 100-66-3 methoxybenzene 
• 90-27-7 2-Phenylbutyric acid 
• 19076-79-0 (E/Z)-1-Bromo-2-[4-[2-(dimethylamino)ethoxy]phenyl]-1,2-diphenylethene 

Downstream Products

• 10540-29-1 tamoxifen 
• 109640-21-3 rel-(1R,2S)-1-<4-<2-(dimethylamino)ethoxy>phenyl>-1,2-diphenylbutane 
• 31750-47-7 {2-[4-((E)-1,2-Diphenyl-but-1-enyl)-phenoxy]-ethyl}-methyl-amine 

Relevant articles and documents

Rh-Catalyzed Coupling of Aldehydes with Allylboronates Enables Facile Access to Ketones

We present herein a novel strategy for the preparation of ketones from aldehydes and allylic boronic esters. This reaction involves the allylation of aldehydes with allylic boronic esters and the Rh-catalyzed chain-walking of homoallylic alcohols. The key to this successful development is the protodeboronation of alkenyl borylether intermediate via a tetravalent borate anion species in the presence of KHF2 and MeOH. This approach features mild reaction conditions, broad substrate scope, and excellent functional group tolerance. Mechanistic studies also supported that the tandem allylation and chain-walking process were involved.

Pd-catalyzed cross-coupling of highly sterically congested enol carbamates with grignard reagents via c-o bond activation

The palladium-catalyzed cross-coupling reaction of enol carbamates to construct highly sterically congested alkenyl compounds is presented for the first time. This protocol demonstrates the potential of using thermally stable and highly atom-economic enol electrophiles as building blocks in bulky alkene synthesis. This reaction accommodates a broad substrate scope with excellent Z/E isomer ratios, which also provides a new synthetic pathway for accessing Tamoxifen.

An atom efficient synthesis of tamoxifen

The direct carbolithiation of diphenylacetylenes and their cross-coupling procedure taking advantage of the intermediate alkenyllithium reagents are presented. By employing our recently discovered highly active palladium nanoparticle based catalyst, we were able to couple an alkenyllithium reagent with a high (Z/E) selectivity (10:1) and good yield to give the breast cancer drug tamoxifen in just 2 steps from commercially available starting materials and with excellent atom economy and reaction mass efficiency.