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

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

Uses

Used in Pharmaceutical Industry:
X-PHOS is used as a reagent for the synthesis of novel [1,2,4]triazolo[4,3-a]pyrazine derivatives, which are potential selective c-met inhibitors. These derivatives have improved pharmacokinetic properties, making them promising candidates for the development of new drugs in the pharmaceutical industry.
Used in Chemical Synthesis:
X-PHOS is used as an exceptional ligand for Pd-catalyzed amination and amidation of aryl sulfonates. Its unique properties make it a valuable component in the synthesis of various complex organic compounds, contributing to the advancement of chemical research and development.
Used in Suzuki Reaction:
X-PHOS is also utilized in the Suzuki reaction, a widely used method for the formation of carbon-carbon bonds in organic chemistry. Its application in this reaction enhances the efficiency and selectivity of the process, leading to the production of desired products with improved yields and reduced side reactions.

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.

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

• 890313-93-6 tert-butyl 2-(benzamido)-4-(1H-indol-1-yl)benzoate 
• 890313-98-1 tert-butyl 2-(benzamido)-4-(2-nitroanilino)benzoate 
• 890313-92-5 tert-butyl 2-(benzamido)-4-(1H-pyrrol-1-yl)benzoate 
• 890316-93-5 tert-butyl 2-(benzamido)-4-(4-phenylpiperidin-1-yl)benzoate 
• 854045-94-6 chloro[2-dicyclohexyl(2′,4′,6′-triisopropylbiphenyl)phosphine]gold(I) 
• 1028206-56-5 chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II) methyl-t-butyl ether adduct 
• 1054612-48-4 [PtCl₂(2-dicyclohexyl-phosphino-2',4',6'-triisopropylbiphenyl)2] 
• 1109286-86-3 [((2',4',6'-triisopropyl-2-biphenyl)dicyclohexylphosphine)Ag(acetate)] 
• 1005787-51-8 N-{3-[(2-anilinoimidazo[1,2-b]pyridazin-6-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide 
• 1005785-62-5 N-[3-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-b]pyridazin-6-yl}amino)phenyl]-1,3-dimethyl-1H-pyrazole-5-carboxamide 
• 1234888-60-8 dicyclohexyl(2',6'-diisopropyl-4'-sulfobiphenyl-2-yl)phosphonium hydrogen sulfate 
• 1233777-95-1 C₃₃H₄₉O₂P 
• 1233777-94-0 C₃₃H₄₉O₂P 
• 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 

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