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Structure of 30309-80-9
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
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CAS No. : | 30309-80-9 |
Formula : | C14H15OP |
M.W : | 230.24 |
SMILES Code : | CC1=CC=CC=C1P(C2=CC=CC=C2C)=O |
MDL No. : | MFCD06754096 |
InChI Key : | PSUGZNIRWGKEPG-UHFFFAOYSA-N |
Pubchem ID : | 15751683 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H315-H317-H319-H335-H360 |
Precautionary Statements: | P201-P261-P280-P305+P351+P338-P308+P313 |
Class: | 6.1 |
UN#: | 2811 |
Packing Group: | Ⅲ |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With palladium diacetate; N-ethyl-N,N-diisopropylamine; 1,4-di(diphenylphosphino)-butane; In dimethyl sulfoxide; at 120℃; for 12h;Inert atmosphere; | (R)-1,1'-Binaphthyl-2,2'-diyl-bis-trifluoromethanesulfonate 18 (0.60 g, 1 mmol) was added to a stirred solution of bis-(2-methylphenyl)-phosphine oxide (0.60 g, 3 mmol), palladium acetate (0.06 g, 0.3 mmol) and diphenylphosphoryl butane (0.10 g, 0.3 mmol) under an atmosphere of argon. N,N-Diisopropylethylamine (0.70 g, 1.0 cm3, 6 mmol) was added dropwise and the reaction mixture heated to 120 C for 12 h. Upon cooling to room temperature, the solution was diluted with ethyl acetate (50 cm3) and washed successively with water (3 * 20 cm3), 1 N HCl (20 cm3) and an aqueous saturated solution of NaHCO3 (20 cm3). The organic layer was dried over magnesium sulfate, filtered, and the solvent removed in vacuo to yield an orange oil. Purification of the crude material by flash column chromatography on silica gel using an eluent of 40% ethyl acetate: petroleum ether 40-60 C afforded the title compound as a white crystalline solid (630 mg, 74%); m.p. 78 C (lit [39]. 123-125 C); [α]25D +62.2 (c 0.5 in CHCl3, lit [39]). +9.1 (c 0.99, CHCl3); δH (400 MHz, CDCl3) 2.15 (3H, s, CH3), 2.48 (3H, s, CH3), 6.90-7.13 (7H, m, ArCH), 7.25-7.31 (3H, m, ArCH), 7.35-7.45 (5H, m, ArCH), 7.61 (1H, app. t, J 7.1, ArCH), 7.87 (1H, app. d, J 8.1, ArCH), 7.97-8.01 (3H, m, ArCH); δF (235 MHz, CDCl3) -75.0; δP (101 MHz, CDCl3) 33.9. Data is in general agreement with the literature. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ethanol; (Dichloroiodo)benzene; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: Into a round bottom flask was added (dichloroiodo)benzene (2, 0.15 mmol, 1.02 equiv), DCM (0.25 mL, 0.6M), and to this was added excess ethanol (0.1 mL, 10 equiv), followed by the secondary phosphine oxide (0.15 mmol, 1.0 equiv,). The reaction mixture was stirred at room temperature for the indicated length of time, then concentrated in vacuo and purified by column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39.9% | Reference Example 9 bis(2-methylphenyl)phosphine oxide Under an argon atmosphere, a solution of magnesium (3.55 g, 1.0 equivalent) and a small amount of iodine in THF (40 ML) was stirred at room temperature for 1 hr.. A solution of o-tolyl bromide (25 g, 0.146 MoL) in THF (5 ML) was added at 30C. After stirring at 40C for 30 min., the mixture was stirred at 5C for 1 hr.. Then, a solution of diethyl phosphite (10.08 g, 0.5 equivalent) in THF (10 ML) was added at 5C, and the mixture was stirred at 5C for 1 hr.. water (20 ML) was added at 3C, and then toluene (50 ML) and 6M-HCl (20 ML) were added.. The mixture was stirred at room temperature for 30 min.. The reaction mixture was partitioned, and the organic layer was washed successively with water (10 ML), 5% aqueous NaHCO3 solution (10 ML) and 5% aqueous NaCl solution (10 ML).. Then the organic layer was dried over anhydrous magnesium sulfate, filtered by gravity, and the filtrate was concentrated under reduced pressure.. The residue was recrystallized from heptane to give the title compound (6.70 g, white crystals).. yield 39.9%. melting point: 91.3C.1H-NMR (300 MHz, CDCl3, TMS) δ: 2.37 (s, 6H), 7.18-7.26 (m, 2H), 7.29-7.34 (m, 2H), 7.43-7.48 (m, 2H), 7.70 (d, 1H, J = 15.06Hz), 7.72 (d, 1H, J = 14.82Hz), 8.21 (d, 1H, J = 476.9 Hz).13C-NMR (75 MHz, CDCl3, CDCl3) δ: 20.59, 126.36, 126.53, 129.04, 130.36, 131.55, 131.69, 132.76, 132.93, 141.44, 141.57.31P-NMR (121 MHz, CDCl3, 85%H3PO4) δ: 16.66-17.93 (m), 20.26-21.86 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43.0% | Example 12 bis(2-methylphenyl)phosphine-borane complex Under an argon atmosphere, a solution of cerium chloride (8.66 g, 3.0 equivalents) in THF (80 ML) was stirred at room temperature (25C) for 30 min.. sodium borohydride (1.37 g, 3.1 equivalents) was added, and the mixture was stirred at room temperature for 1 hr.. Then <strong>[30309-80-9]bis(2-methylphenyl)phosphine oxide</strong> (2.7 g, 11.72 MmoL) synthesised in Reference Example 9 and lithium aluminum hydride (0.53 g, 1.2 equivalents) were successively added at 5C, and the mixture was stirred at room temperature for 4 hrs.. toluene (80 ML) was added at 3C, and then 3M-HC1 (30 ML) was added.. The mixture was stirred at room temperature for 30 min.. The reaction mixture was partitioned, and the aqueous layer was extracted with toluene (20 ML).. The combined organic layer was washed with 5% aqueous NaCl solution (20 ML).. The organic layer was dried over anhydrous magnesium sulfate, filtered by gravity, and the filtrate was concentrated under reduced pressure.. toluene (20 ML) and silica gel (10 g) were added to the residue and the mixture was stirred at room temperature for 10 min.. The mixture was filtered by gravity, and the filtrate was concentrated under reduced pressure. THF (5 ML) and BH3·THF (5 ML) were added to the residue at 5C, and the mixture was stirred at room temperature for 1 hr.. The mixture was concentrated under reduced pressure and the residue was recrystallized from heptane to give the title compound (1.15 g, white crystals).. yield 43.0%. melting point: 78.0C.1H-NMR (300 MHz, CDCl3, TMS) δ: 0.42-1.63 (m, 3H), 2.32 (s, 6H), 6.47 (dq, 1H, J = 377.5 Hz, 6.63 Hz), 7.21-7.31 (m, 4H), 7.38-7.43 (m, 2H), 7.59 (d, 1H, J = 13.56Hz), 7.61 (d, 1H, J = 13.53Hz).13C-NMR (75 MHz, CDCl3, CDCl3) δ: 20.81, 20.88, 126.36, 126.52, 130.85, 130.95, 131.67, 131.70, 133.82, 134.01, 141.42.31P-NMR (121 MHz, CDCl3, 85%H3PO4) δ: -15.58- -14.22 (m), -12.67- -11.33 (m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
23%; 47% | With silver(I) acetate; In dimethyl sulfoxide; at 120℃; for 12h;Inert atmosphere; | General procedure: A suspension of phosphinate 1a (85 mg, 0.50 mmol), diphenylacetylene(2a; 178 mg, 1.00 mmol), AgOAc (167.0 mg, 1.00 mmol) inDMSO (2.0 mL) was stirred under N2 atmosphere at r.t., and then at 120 C for 12 h. At r.t., the reaction mixture was diluted with H2O(10 mL) and extracted with EtOAc (3 ~ 25 mL). The combined organiclayers were dried (Na2SO4). After filtration and evaporationof the solvents in vacuo, the crude product was purified by columnchromatography on silica gel (n-hexane.EtOAc, 5:1 2:1) to afford3aa as an off-white oil; yield: 104 mg (60%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With sodium fluoride; trifluoroacetic anhydride; In dimethyl sulfoxide; acetonitrile; at 100℃; for 11h;Inert atmosphere; | Take bis(2-methylphenyl)phosphorus oxide (69mg, 0.3mmol) and sodium fluoride (25.2mg, 0.6mmol) into a 10mL reaction tube. Use a double-row tube to replace the air in the reaction tube with nitrogen. Three times, then 2mL of acetonitrile, trifluoroacetic anhydride (157.5mg, 0.75mmol), DMSO (47.9mg, 0.6mmol) were sequentially added to it, and the reaction was placed in an oil bath at 100C for 11 hours. After the reaction, the reaction solution was concentrated, and the mixture of petroleum ether and ethyl acetate with a volume ratio of 3:1 was used as the eluent. The product was separated by column chromatography to obtain the product bis(2-methylphenyl)phosphoryl fluoride. The yield was 88%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; at 0 - 20℃; for 24h; | General procedure: The synthesis of α-aminoalkylphosphine oxides startedwith the preparation of diaryl or dialkyl phosphine oxidesobtained via the oxidation of diaryl or dialkylchlorophosphines with 1 M HClaq (0 C → r.t., 24 h).The resulting crude phosphine oxide (1 eq.) was dissolvedin toluene, and a tritylimine (1 eq.) was added. The reactionwas performed under reflux for 8 h. The volatilecomponents were removed under vacuum, and the tritylprotecting group was removed with TFA (2 h, r.t.) for thearyl derivatives or HCl (10 eq.) in MeOH (30 min, reflux)for the alkyl derivatives. The crude products were used inthe next steps of peptidyl derivative preparation. The synthesisof the α-aminoalkylphosphine oxides is outlined inFig. 9a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | In toluene; at 60℃;Inert atmosphere; Green chemistry; | General procedure: A solution of the 3-diazooxindole (0.3 mmol) in toluene (1.2 mL) wasslowly added to a solution of H-phosphine oxide (0.6 mmol) in toluene(1.2 mL). The reaction mixture was stirred at 60 C under an argonatmosphere. After reaction completion (TLC monitoring), the solutionwas concentrated in vacuo. The residue was purified by columnchromatography on silica gel (petroleum ether/ethyl acetate 1:1) toafford compounds 3a-r. |