564483-18-7

Basic information

• Product Name: X-PHOS
• Synonyms: X-PHOS;5-BROMO-4-CHLORO-3-INDOLYL PHOSPHATE;2-(DICYCLOHEXYLPHOSPHINO)-2',4',6'-TRI-I-PROPYL-1,1'-BIPHENYL;2-DICYCLOHEXYLPHOSPHINO-2',4',6'-TRIISO-PROPYL-1,1'-BIPHENYL;2-DICYCLOHEXYLPHOSPHINO-2',4',6'-TRIISOPROPYLBIPHENYL;2-Dicyclohexylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl, X-PHOS;2-(Dicyclohexylphosphino)-2',4',6'-tri-i-propyl-1,1'-biphenyl,min.98%X-Phos;2-Dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl, 98+%
• CAS NO: 564483-18-7
• Molecular Formula: C₃₃H₄₉P
• Molecular Weight: 476.72
• EINECS: 270-588-3
• Product Categories: Achiral Phosphine;Aryl Phosphine;Buchwald Ligands Series;Buchwald Ligands&Precatalysts
• Mol File: 564483-18-7.mol
• Article Data: 6

Chemical Properties

• Melting Point: 187-190 °C(lit.)
• Boiling Point: 569.762 °C at 760 mmHg
• Flash Point: 317.745 °C
• Appearance: white/Powder
• Storage Temp.: Inert atmosphere,Room Temperature
• Solubility: Benzene (Slightly)
• Sensitive: Air Sensitive
• Stability: Air Sensitive
• CAS DataBase Reference: X-PHOS(CAS DataBase Reference)
• NIST Chemistry Reference: X-PHOS(564483-18-7)
• EPA Substance Registry System: X-PHOS(564483-18-7)

Safety Data

• Hazard Codes: Xn
• Statements: 36/37/38-22-40
• Safety Statements: 37/39-26-36/37
• WGK Germany: 3
• TSCA: No
• Hazardous Substances Data: 564483-18-7(Hazardous Substances Data)

Usage

Reaction

Exceptional ligands for Pd-catalyzed amination and amidation of aryl sulfonates. ?Ligand used for the Pd-catalyzed Suzuki-Miyaura coupling reaction and carbonyl enolate coupling. ?Ligand used for the chemoselective amination of aryl chlorides. ?Ligand used for the Pd-catalyzed borylation of aryl chlorides, for the formation of trifluoroborates. ?Ligand used for the Pd-catalyzed amination of vinyl halides and triflates. ?Ligand used for the Pd-catalyzed three-component synthesis of indoles. ?Ligand used for the Pt-catalyzed regioselective hydrosilylation of functionalized terminal arylalkynes. ?Ligand used for the Pd-catalyzed synthesis of carbazoles. ?Ligand used for the Pd-catalyzed Suzuki-Miyaura coupling of aryl chloride and NHC-boranes. ?Ligand used for the direct arylation of picoline N-oxide. ?Ligand used for the Negishi coupling of 2-heterocyclic organozinc reagents. ?Catalyst for a phosphine-catalyzed Heine reaction. ?Ligand used for the palladium-catalyzed oxidative coupling of indoles and heteroarenes. ?Ligand used for the silver-catalyzed hydrogenation of aldehydes. ?Ligand used for the palladium-catalyzed cyanation of heterycyclic halides.

Chemical Properties

White crystalline powder

Uses

Different sources of media describe the Uses of 564483-18-7 differently. You can refer to the following data:
1. suzuki reaction
2. Exceptional ligands for Pd-catalyzed amination and amidation of aryl sulfonates. XPHOS is used as a regent in the synthesis of novel [1,2,4]triazolo[4,3-a]pyrazine derivatives as potential selective c-met inhibitors with improved pharmacokinetic properties.
3. XPHOS is used as a regent in the synthesis of novel [1,2,4]triazolo[4,3-a]pyrazine derivatives as potential selective c-met inhibitors with improved pharmacokinetic properties.

General Description

This product has been enhanced for catalytic efficiency.

Synthetic route

fluorobenzene (462-06-6) + 1,3,5-triisopropyl benzene (717-74-8) + chlorodicyclohexylphosphane (16523-54-9) → XPhos (564483-18-7)

Conditions	Yield
Stage #1: fluorobenzene With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: chlorodicyclohexylphosphane In tetrahydrofuran at 15℃; for 10h; Stage #3: 1,3,5-triisopropyl benzene With n-butyllithium; potassium tert-butylate In hexane at 30 - 60℃; for 16h; Reagent/catalyst; Temperature;	93%

2'-chloro-2,4,6-triisopropylbiphenyl + chlorodicyclohexylphosphane (16523-54-9) → XPhos (564483-18-7)

Conditions	Yield
Stage #1: 2'-chloro-2,4,6-triisopropylbiphenyl With n-butyllithium at 0℃; for 1h; Stage #2: chlorodicyclohexylphosphane at 20℃; for 2h; Temperature; Reagent/catalyst;	90%

1-Bromo-2,4,6-triisopropylbenzene (21524-34-5) + chlorodicyclohexylphosphane (16523-54-9) + 1,2-dibromobenzene (583-53-9) → XPhos (564483-18-7)

Conditions	Yield
Stage #1: 2,4,6-triisopropyl-1-bromobenzene With n-butyllithium In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #2: 2,3-dibromobenzene In tetrahydrofuran at 0℃; for 1h; Inert atmosphere; Stage #3: chlorodicyclohexylphosphane Further stages;	89%

2-bromo-1-chlorobenzene (694-80-4) + 1-Bromo-2,4,6-triisopropylbenzene (21524-34-5) + dicyclohexylbromophosphine (100384-03-0) → XPhos (564483-18-7)

Conditions	Yield
Stage #1: 2,4,6-triisopropyl-1-bromobenzene With magnesium; ethylene dibromide In tetrahydrofuran at 65℃; Inert atmosphere; Stage #2: 2-bromo-1-chlorobenzene In tetrahydrofuran at 65℃; for 2h; Stage #3: dicyclohexylbromophosphine With copper(l) chloride In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;	86%

2-bromo-1-chlorobenzene (694-80-4) + 1-Bromo-2,4,6-triisopropylbenzene (21524-34-5) + chlorodicyclohexylphosphane (16523-54-9) → XPhos (564483-18-7)

Conditions	Yield
Stage #1: 2,4,6-triisopropyl-1-bromobenzene With magnesium; ethylene dibromide In tetrahydrofuran at 65℃; for 1h; Stage #2: 2-bromo-1-chlorobenzene In tetrahydrofuran at 65℃; for 1h; Stage #3: chlorodicyclohexylphosphane With copper(l) chloride In tetrahydrofuran at 20℃; for 20h;	83%
Stage #1: 2,4,6-triisopropyl-1-bromobenzene With magnesium; ethylene dibromide In tetrahydrofuran at 65℃; Inert atmosphere; Stage #2: 2-bromo-1-chlorobenzene In tetrahydrofuran at 65℃; for 2h; Stage #3: chlorodicyclohexylphosphane With copper(l) chloride In tetrahydrofuran at 20℃; for 10h; Inert atmosphere;	83%
Stage #1: 2,4,6-triisopropyl-1-bromobenzene With magnesium; ethylene dibromide In tetrahydrofuran for 2h; Inert atmosphere; Reflux; Industrial scale; Stage #2: 2-bromo-1-chlorobenzene With magnesium In tetrahydrofuran for 2h; Inert atmosphere; Reflux; Industrial scale; Stage #3: chlorodicyclohexylphosphane With copper(l) chloride In tetrahydrofuran at 20℃; Thermodynamic data; Inert atmosphere; Industrial scale;	56%

(tetrahydrothiophene)gold(I) chloride (39929-21-0) + XPhos (564483-18-7) → chloro[2-dicyclohexyl(2′,4′,6′-triisopropylbiphenyl)phosphine]gold(I) (854045-94-6)

Conditions	Yield
In dichloromethane for 1.75h;	99%
In toluene (N2); Au complex added to a soln. of ligand, stirred for 20 h; evapd. (vac.), pentane added, the solid collected, dried; elem. anal.;	91%
In dichloromethane Inert atmosphere;
In dichloromethane
In dichloromethane at 20℃; for 1h; Darkness;

N-phenyl-2-aminobiphenylpalladium methanesulfonate (1599466-80-4) + XPhos (564483-18-7) → C52H66NO3PPdS (1599466-82-6)

Conditions	Yield
In dichloromethane at 20℃; for 1h;	99%

XPhos (564483-18-7) → dicyclohexyl(2',6'-diisopropyl-4'-sulfobiphenyl-2-yl)phosphonium hydrogen sulfate (1234888-60-8)

Conditions	Yield
With sulfuric acid; sulfur trioxide at -40 - 20℃; Inert atmosphere;	98%

4-bromo-1,1'-biphenyl (92-66-0) + 4-dibenzothiophene boronic acid (108847-20-7) + XPhos (564483-18-7) → 4-([1,1'-biphenyl]-4-yl)dibenzo[b,d]thiophene

Conditions	Yield
With tris-(dibenzylideneacetone)dipalladium(0)	98%

C12H10ClNPd + XPhos (564483-18-7) → 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

Conditions	Yield
In acetone at 25℃;	97%

bis(η3-allyl-μ-chloropalladium(II)) + XPhos (564483-18-7) → [2,6-bis(2,4,6-triisopropylphenyl)phenyl(dicyclohexylphosphine)](allyl-η3)palladium(II) chloride

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h; Schlenk technique; Inert atmosphere;	97%
In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;	97%
In diethyl ether at 25℃; for 1h; Inert atmosphere; Schlenk technique;	53%

XPhos (564483-18-7) → dichloro[η6 :η1-dicyclohexyl-(2',4',6'-triisopropylbiphenyl-2-yl)phosphane]ruthenium(II)

Conditions	Yield
With [RuCl2(cod)]n In 1-methyl-pyrrolidin-2-one at 120℃; for 24h; Inert atmosphere;	95%

[Pd2(CH3CN)6][BF4]2 + XPhos (564483-18-7) → C66H98P2Pd2(2+)*2BF4(1-)

Conditions	Yield
In dichloromethane at 20℃; for 0.5h;	95%

XPhos (564483-18-7) → sodium 2'‐(dicyclohexylphosphaneyl)‐2,6‐diisopropyl‐[1,1'‐biphenyl]‐4‐sulfonate

Conditions	Yield
Stage #1: XPhos With sulfuric acid; sulfur trioxide In dichloromethane at 0 - 20℃; for 24h; Cooling with ice; Stage #2: With sodium hydroxide In dichloromethane; water at 0℃; pH=~ 7.0; Cooling with ice;	94%
Stage #1: XPhos With sulfuric acid In dichloromethane at 0℃; for 0.0833333h; Sealed tube; Schlenk technique; Inert atmosphere; Stage #2: With fuming sulphuric acid In dichloromethane at -10℃; for 0.216667h; Schlenk technique; Sealed tube; Inert atmosphere; Stage #3: With sodium hydroxide In dichloromethane; water for 0.283333h; pH=14; Cooling with ice; regioselective reaction;	77%
Stage #1: XPhos With sulfuric acid In dichloromethane at 0 - 20℃; for 24h; Stage #2: With sodium hydroxide In dichloromethane; water pH=13;	53%

(2'-amino-1,1'-biphenyl-2-yl)methanesulfonatopalladium(II) dimer (1435520-65-2) + XPhos (564483-18-7) → ((2-dicyclohexylphosphino-2',4’,6’-triisopropyl-1,1‘-biphenyl)[2-(2‘-amino-1,1‘-biphenyl)]palladium(II) methanesulfonate) (1445085-55-1, 1445085-72-2)

Conditions	Yield
In tetrahydrofuran at 20℃;	92%

di(2-(2′-amino-1,1′-biphenyl))palladium(II) methanesulfonate dimer + XPhos (564483-18-7) → methanesulfonic acid(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) (1445085-55-1, 1445085-72-2)

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.75h; Inert atmosphere;	92%

N1,N1-diphenyl-1,3-phenylenediamine (116724-06-2) + methyl(3-iodopyridin-2-yl)amine (113975-23-8) + sodium t-butanolate (865-48-5) + XPhos (564483-18-7) → N3-(3-(diphenylamino)phenyl)-N2-methylpyridine-2,3-diamine (1399050-27-1)

Conditions	Yield
With nitrogen In dichloromethane; ethyl acetate; toluene	91%

bis[(1,2,3-η)-2-butenyl]di(μ-chloro)palladium(II) + XPhos (564483-18-7) → chloro(crotyl)(2-dicyclohexylphosphino-2’,4’,6’-triisopropybiphenyl)palladium(II)

Conditions	Yield
In tetrahydrofuran at 20℃; for 3h; Schlenk technique; Inert atmosphere;	91%
In toluene at 20℃; for 2h; Inert atmosphere;	91%

(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one palladium(II) complex + 4-fluoro-1-iodobenzene (352-34-1) + XPhos (564483-18-7) → (4-F-C6H4)Pd(XPhos)I

Conditions	Yield
In toluene at 20℃; Inert atmosphere;	91%

dihydrogen tetrachloropalladate(II) + XPhos (564483-18-7) → [HXPhos]2[Pd2Cl6]

Conditions	Yield
With hydrogenchloride In water; acetone at 18 - 27℃; for 1h;	91%

(N,N,N',N'-tetramethylethylenediamine)dimethylpalladium(II) + 2-(2-chlorophenyl)ethanamine (13078-80-3) + XPhos (564483-18-7) → chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct (1028206-56-5)

Conditions	Yield
In further solvent(s) treatment of palladium compd. with chlorobenzene deriv. and phosphine deriv. in methyl tert-butyl ether at 55°C; recrystn.;	90%

bis(acetonitrile)(acetylacetonate)palladium(II) tetrafluoroborate + XPhos (564483-18-7) → (acetylacetonate-κ2O,O')(2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl-κP)palladium(II) tetrafluoroborate

Conditions	Yield
In dichloromethane at 20℃; for 2h;	87.7%

[Pd(η3-tBu-indenyl)(μ-Cl)]2 + XPhos (564483-18-7) → C46H64ClPPd

Conditions	Yield
at 20℃; for 1h; Inert atmosphere;	86%

η3-1-tert-butylindenyl palladium chloride dimer + XPhos (564483-18-7) → C46H64ClPPd

Conditions	Yield
In tetrahydrofuran for 1h; Inert atmosphere; Schlenk technique;	86%

(2′-methylamino-1,1′-biphenyl-2-yl)methanesulfonatopalladium(II) dimer (1581285-85-9) + XPhos (564483-18-7) → (2‑dicyclohexylphosphino‑2′,4′,6′‑triisopropyl‑1,1′‑biphenyl)[2‑(2′‑methylamino‑1,1′‑biphenyl)]palladium(II) methanesulfonate (1599466-81-5)

Conditions	Yield
In dichloromethane at 20℃; for 1h;	85%

iodobenzene (591-50-4) + bis[(trimethylsilyl)methyl](1,5-cyclooctadiene)palladium(II) (225931-80-6) + XPhos (564483-18-7) → C33H49P*C6H5(1-)*Pd(2+)*I(1-)

Conditions	Yield
In pentane at 20℃; for 72h; Glovebox; Inert atmosphere;	85%

lithium tetrachloropalladate + C49H38CuN3OP2 + XPhos (564483-18-7) → C82H86ClCuN3OP3Pd

Conditions	Yield
Stage #1: lithium tetrachloropalladate; C49H38CuN3OP2 With sodium acetate In methanol at 23℃; for 24h; Stage #2: XPhos In acetone at 25℃; for 3h;	85%

bis(μ-chloro)bis(η3-indenyl)dipalladium(II) (90624-27-4) + silver trifluoromethanesulfonate (2923-28-6) + XPhos (564483-18-7) → (η3-indenyl)Pd(XPhos)(OTf)

Conditions	Yield
In tetrahydrofuran at 20℃; for 0.5h; Schlenk technique;	85%

palladium diacetate (3375-31-3) + 2-phenylaniline (90-41-5) + lithium chloride + XPhos (564483-18-7) → (chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II)) (1310584-14-5)

Conditions	Yield
In toluene NH2C6H4C6H5 reacted with Pd salt in toluene at 60°C, reacted withLiCl in acetone at room temp., reacted with (C6H11)2PC6H4C6H2(CH(CH3)2) 3 at room temp.;	83%

[Pd(μ-Cl)(Cl)(N,N′-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene)]2 + XPhos (564483-18-7) → [PdCl2(N,N′-bis-(2,6-diisopropylphenyl)imidazol-2-ylidene)(PCy2(2',4',6'-iPr3-2-byphenyl))]

Conditions	Yield
In tetrahydrofuran for 3h; Schlenk technique; Inert atmosphere; Glovebox;	83%

Upstream product

• 694-80-4 2-bromo-1-chlorobenzene 
• 21524-34-5 2,4,6-triisopropyl-1-bromobenzene 
• 16523-54-9 chlorodicyclohexylphosphane 
• 100384-03-0 dicyclohexylbromophosphine 
• 583-53-9 2,3-dibromobenzene 
• 462-06-6 fluorobenzene 
• 717-74-8 1,3,5-triisopropyl benzene 
• 109-06-8 α-picoline 

Downstream Products

• 1233777-95-1 C₃₃H₄₉O₂P 
• 1233777-94-0 C₃₃H₄₉O₂P 
• 1252575-64-6 N-(2,5-difluoro-4-(morpholinomethyl)phenyl)-5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine 
• 1252575-67-9 N-(2,5-difluoro-4-(morpholinomethyl)phenyl)-5-fluoro-4-(2-methyl-1-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-5-yl)pyrimidin-2-amine hydrochloride 
• 1225015-88-2 7-(3-hydroxy-prop-1-ynyl)-3-(4-methoxyphenyl)chromen-2-one 
• 1353896-96-4 C₁₈HBF₁₅^(1-)*C₃₃H₄₉P*H⁽¹⁺⁾ 
• 1599466-81-5 (2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2′-amino-1,1′-biphenyl)]palladium(II) methanesulfonate 
• 1599466-82-6 C₅₂H₆₆NO₃PPdS 
• 1246382-80-8 6,6'-(3-chloro-4-(3-(2-chloropyridin-4-yl)-4,4,4-trifluoro-3-hydroxybutan-2-yl)phenylazanediyl)dinicotinic acid dimethyl ester 
• 1005785-62-5 N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}amino)phenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide 
• 1005787-51-8 N-{3-[(2-anilinoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide 
• 1054612-48-4 [PtCl₂(2-dicyclohexyl-phosphino-2',4',6'-triisopropylbiphenyl)2] 
• 1028206-56-5 chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct 
• 869335-77-3 N-(2-fluoro-4-nitrophenyl)-3-(trifluoromethyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-4-amine 

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