BIS(DI-TERT-BUTYL(4-DIMETHYLAMINOPHENYL)PHOSPHINE)DICHLOROPALLADIUM(II)

Yellow powder

To a 500 mL reaction was added 10 g (1, 5-cyclooctadiene) palladium dichloride, the reaction flask was replaced with a nitrogen atmosphere, 19.6 g of di-tert-butyl-4-dimethylaminophenylphosphine prepared in and 200 mL of anhydrous tetrahydrofuran were added, and the mixture was stirred at room temperature for 16 hours, There is a solid precipitation, Filtration and drying gave a pale yellow powder product bis (di-tert-butyl-4-dimethylaminophenylphosphine) palladium chloride 24. 1 g, The yield was 97percent (yield based on (1, 5-cyclooctadiene) palladium dichloride)The purity of the product was 99.8percent by XY-1A intelligent element analyzer.Take a dry 10L three-neck reaction flask, dry nitrogen is fully replaced and under nitrogen flow protection, Add 5.5 L of anhydrous tetrahydrofuran, stir and add 540 g of bis(acetonitrile)palladium dichloride.The obtained ligand di-tert-butyl-4-dimethylaminophenylphosphine was further reacted for 30 minutes, and a yellow solid was precipitated. After the reaction was continued for 9 hours at room temperature, After filtration, the filter cake was dipped in anhydrous tetrahydrofuran, drained and dried in a vacuum oven at 60 ° C.Obtaining a yellow crystalline powdery target product, namely dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium, yielding 1440 g to 1445 g, Elemental analysis showed that the product content exceeded 98.0percent, the palladium content exceeded 15.0percent, and the palladium calculated yield was 97.7percent to 98.1percent.Step 14-6, Preparation of tert-butyl N-{3-[(4-{4-[2-cyano-4-(trifluoromethyl)phenyl]piperazin-1-yl}-2'-ethoxy-[1, 1'-biphenyl]-3-yl)formamido]propyl}carbamate To a mixture of tert-butyl N-{3-[(5-bromo-2-{4-[2-cyano-4-(trifluoromethyl)phenyl]piperazin-1-yl}phenyl)formamido]propyl}carbamate (20.0 mg, 0.0328 mmol), 2-ethoxyphenylboronic acid (10.9 mg, 0.0657 mmol), Pd[t-Bu2P(4-NMe2C6H4)]2Cl2) (9.2 mg, 0.013 mmol), and K2CO3 (27.2 mg, 0.197 mmol) in a sealed tube was added dioxane (2 mL) and H2O (0.2 mL). The resulting mixture was degassed with N2 for 10 min and stirred at 100 C. for 30 min. The mixture was concentrated and purified by C18 reversed phase column chromatography to give the title compound (18.5 mg, 87% yield) as a white solid. LCMS (M+H)+=652.5.Step 3-4, Preparation of tert-butyl (3R)-4-[4-(2-ethoxypyridin-3-yl)-3-fluoro-2-(methoxycarbonyl)phenyl]-3-ethylpiperazine-1-carboxylate To a mixture of tert-butyl (3R)-4-[4-bromo-3-fluoro-2-(methoxycarbonyl)phenyl]-3-ethylpiperazine-1-carboxylate (267 mg, 0.600 mmol), (2-ethoxypyridin-3-yl)boronic acid (150 mg, 0.900 mmol), Pd[t-Bu2P(4-NMe2C6H4)]2Cl2) (42.5 mg, 0.0600 mmol), and K2CO3 (249 mg, 1.80 mmol) in a sealed tube was added dioxane (4 mL) and H2O (0.4 mL). The resulting solution was degassed with N2 (g) for 10 min, sealed, and stirred at 100 C. for 30 min. The reaction was treated with additional (2-ethoxypyridin-3-yl)boronic acid (37.8 mg, 0.226 mmol), Pd[t-Bu2P(4-NMe2C6H4)]2Cl2) (13.4 mg, 0.0189 mmol), and K2CO3 (78.3 mg, 0.567 mmol) and stirred at 100 C. for additional 30 min. The mixture was concentrated and purified by C18 reversed phase column chromatography to give the title compound (255 mg, 87% yield) as a brown gum. LCMS (M+H)+: 488.4.Take a dry 10L three-neck reaction flask, dry nitrogen is fully replaced and under nitrogen flow protection, Add 5.5 L of anhydrous tetrahydrofuran, stir and add 540 g of bis(acetonitrile)palladium dichloride.The obtained ligand di-tert-butyl-4-dimethylaminophenylphosphine was further reacted for 30 minutes, and a yellow solid was precipitated. After the reaction was continued for 9 hours at room temperature, After filtration, the filter cake was dipped in anhydrous tetrahydrofuran, drained and dried in a vacuum oven at 60 C.Obtaining a yellow crystalline powdery target product, namely dichlorodi-tert-butyl-(4-dimethylaminophenyl)phosphine palladium, yielding 1440 g to 1445 g, Elemental analysis showed that the product content exceeded 98.0%, the palladium content exceeded 15.0%, and the palladium calculated yield was 97.7% to 98.1%.To a 500 mL reaction was added 10 g (1, 5-cyclooctadiene) palladium dichloride, the reaction flask was replaced with a nitrogen atmosphere, 19.6 g of di-tert-butyl-4-dimethylaminophenylphosphine prepared in and 200 mL of anhydrous tetrahydrofuran were added, and the mixture was stirred at room temperature for 16 hours, There is a solid precipitation, Filtration and drying gave a pale yellow powder product bis (di-tert-butyl-4-dimethylaminophenylphosphine) palladium chloride 24. 1 g, The yield was 97% (yield based on (1, 5-cyclooctadiene) palladium dichloride)The purity of the product was 99.8% by XY-1A intelligent element analyzer.

Useful catalyst for the Suzuki Cross-Coupling of dioxolanylethyltrifluorborate and aryl/heteroaryl chlorides

Molecular Weight:708.1
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:8
Exact Mass:706.23306
Monoisotopic Mass:706.23306
Topological Polar Surface Area:6.5
Heavy Atom Count:39
Complexity:240
Covalently-Bonded Unit Count:3
Compound Is Canonicalized:Yes