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Chemical Structure| 30913-86-1 Chemical Structure| 30913-86-1

Structure of 30913-86-1

Chemical Structure| 30913-86-1

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Product Details of [ 30913-86-1 ]

CAS No. :30913-86-1
Formula : C11H11BrO3
M.W : 271.11
SMILES Code : O=C(OC)CCC(C1=CC=C(Br)C=C1)=O
MDL No. :MFCD03090515
InChI Key :NSIXBKXISVRTCO-UHFFFAOYSA-N
Pubchem ID :838865

Safety of [ 30913-86-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 30913-86-1 ] Show Less

Physicochemical Properties

Num. heavy atoms 15
Num. arom. heavy atoms 6
Fraction Csp3 0.27
Num. rotatable bonds 5
Num. H-bond acceptors 3.0
Num. H-bond donors 0.0
Molar Refractivity 60.04
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

43.37 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

2.41
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.43
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.59
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

2.3
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

3.0
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

2.54

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-3.02
Solubility 0.26 mg/ml ; 0.00096 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.98
Solubility 0.282 mg/ml ; 0.00104 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-4.08
Solubility 0.0223 mg/ml ; 0.0000824 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Moderately soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

Yes
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-6.23 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

0.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<0.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.61

Application In Synthesis of [ 30913-86-1 ]

* 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.

  • Downstream synthetic route of [ 30913-86-1 ]

[ 30913-86-1 ] Synthesis Path-Downstream   1~35

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  • [ 30913-86-1 ]
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  • [ 67-56-1 ]
  • [ 6340-79-0 ]
  • [ 30913-86-1 ]
YieldReaction ConditionsOperation in experiment
With sulfuric acid; for 21h;Heating / reflux; Preparation 2 4-(4-Bromophenyl)-4-oxobutyric acid methyl ester [0277] [CHEMMOL-00059] [0278] 4-(4-Bromophenyl)-4-oxobutyric acid (86.4 g, 0.336 mol) (Preparation 1) in MeOH (1.71) containing H2SO4 (86 ml) was refluxed for 21 h. After cooling, the light precipitate was filtered off and the reaction mixture concentrated to dryness. The obtained solid was placed in water and extracted twice with EtOAc. The organic layer was washed with diluted NaOH and twice with brine, dried over Na2SO4 and concentrated to yield the desired 4-(4-bromophenyl)-4-oxobutyric acid methyl ester as a low melting point solid (87.5 g, mp=50 C.). 1H NMR (CDCl3): 7.85 (2H, d, J=8.5 Hz), 7.60 (2H, d, J=8.5 Hz), 3.71 (3H, s), 3.28 (2H, t, J=6.5 Hz), 2.76 (2H, t, J=6.5 Hz).
With thionyl chloride; at 20℃; for 2h; To a solution of 4- (4-bromophenyl) -4-oxobutanoic acid (14.5 g, 56.42 mmol) in CH 3OH (200 mL) was added SOCl 2 (10 mL) slowly, the mixture was stirred at ambient temperature for 2h. The solution was concentrated. The residue was partitioned between DCM (100 mL) and Sat. NaHCO 3 (300 mL). The organic layer was dried over Na 2SO 4 and concentrated to give the crude product as yellow oil. (15.0 g).
  • 6
  • [ 30913-86-1 ]
  • [ 126135-40-8 ]
YieldReaction ConditionsOperation in experiment
In einem Schlenkgefaess wird die Katalysatorloesung durch Einwaage von 2,03 Mol-Aequivalenten 1S,2S-N-(p-Toluolsulfonyl)-1,2-diphenylethylen-diamin (S,S-TsDPEN) und 1 Mol-Aequivalent [(Cumol)RuC12]2, Ruehren dieses Gemisches in 5 ml Dichlormethan und Versetzen mit 2 Mol-Aequivalenten Triethylamin hergestellt. In einem Mehrhalskolben mit Begasungs-Ruehrer, Rueckflusskuehler und Thermometer wird eine Ameisensaeure/Triethylamin-Mischung (Molverhaeltnis 1:1, Molverhaeltnis 1,05:1 bezogen auf das Substrat) durch langsames Zutropfen innerhalb von 5 min per Tropftrichter von Ameisensaeure zum Triethylamin unter Ruehrung und Eiskuehlung hergestellt. Zu diesem zweiphasigen Gemisch wird der entsprechende Ketoverbindung gegeben (100-5000 Aequivalente bezogen auf den Katalysator), die homogene gelbe Loesung gegebenenfalls mit Loesungsmittel versetzt und die Gesamtmischung durch Durchleiten von Argon fuer 20 min entgast. Es wird auf Solltemperatur temperiert und unter starkem Ruehren die dunkelrote Katalysatorloesung auf einmal zum Reaktionsansatz per Spritze geben. Es wird unter Argon fuer die gegebene Zeit geruehrt. Es wird mit Wasser und Dichlormethan verduennt, fuer 10 min nachgeruehrt, nach Phasentrennung die waessrige Phase 2 mal mit Dichlormethan extrahiert. Die vereinigten organischen Phasen werden mit NaCI-Loesung gewaschen, ueber MgSO4 getrocknet, filtriert und dann das Loesungsmittel am Rotationsverdampfer entfernt. Das Rohprodukt wird entweder destilliert, umkristallisiert z.B. aus Hexan/Petrolether bzw. aus Hexan/Dichlormethan oder als Rohmischung in weiteren Reaktionen eingesetzt. Es entsteht ueblicherweise ein Gemisch aus Hydroxyestern und Lactonen in Verhaeltnissen von 99:1 bis 80:20 zugunsten des Hydroxyesters. Die vollstaendige Umwandlung in die entsprechenden Lactone (siehe Formel VII) erfolgt durch Ruehren des Gemisches mit 2 N NaOH-Loesung bei 60C fuer 1 h. Die Umsatz- und Enantiomeren-Analytik erfolgte gaschromatographisch unter Verwendung von Kapillarsaeulen der Firma IVA. 12-25 m Saeulen vom Typ IVADEX 1 (Saeule A), IVADEX 3 (Saeule B) und Hydrodex-beta-6-TBDM (Saeule C) kamen unter Verwendung von Helium als Traegergas auf einem HP 5890 II Gaschromatographen zum Einsatz. Die hier angefuehrten Umsaetze und Reaktionszeiten sind nicht optimiert, da zumeist in geschlossenen Gefaessen ohne Ableitung von CO2 gearbeitet wurde. 1H-NMR (d1-Chloroform, 400 MHz): delta = 7.45 (d, 2H, Ph), 7.14 (d, 2H, Ph), 5.40 (pt, 1H, CHOH), 3.42 (s, 3H, CH3), 2.37 (t, 2H, CH2), 2.20 (br, 1H, OH), 1.98 (pq, 2H, CH2) ppm. ee: 89,9 %, t = 66 h, U = 96 %. S/C = 400, T = 30C. Chiral-GC: Ester: 18,98, 19,64 min, Lacton: 16,20, 17,24 min (Saeule A, 12.5 m, 15 min 160C, 2C/min, 220C).
In einem Schlenkgefaess wird die Katalysatorloesung durch Einwaage von 2,03 Mol-Aequivalenten 1S,2S-N-(p-Toluolsulfonyl)-1,2-diphenylethylen-diamin (S,S-TsDPEN) und 1 Mol-Aequivalent [(Cumol)RuC12]2, Ruehren dieses Gemisches in 5 ml Dichlormethan und Versetzen mit 2 Mol-Aequivalenten Triethylamin hergestellt. In einem Mehrhalskolben mit Begasungs-Ruehrer, Rueckflusskuehler und Thermometer wird eine Ameisensaeure/Triethylamin-Mischung (Molverhaeltnis 1:1, Molverhaeltnis 1,05:1 bezogen auf das Substrat) durch langsames Zutropfen innerhalb von 5 min per Tropftrichter von Ameisensaeure zum Triethylamin unter Ruehrung und Eiskuehlung hergestellt. Zu diesem zweiphasigen Gemisch wird der entsprechende Ketoverbindung gegeben (100-5000 Aequivalente bezogen auf den Katalysator), die homogene gelbe Loesung gegebenenfalls mit Loesungsmittel versetzt und die Gesamtmischung durch Durchleiten von Argon fuer 20 min entgast. Es wird auf Solltemperatur temperiert und unter starkem Ruehren die dunkelrote Katalysatorloesung auf einmal zum Reaktionsansatz per Spritze geben. Es wird unter Argon fuer die gegebene Zeit geruehrt. Es wird mit Wasser und Dichlormethan verduennt, fuer 10 min nachgeruehrt, nach Phasentrennung die waessrige Phase 2 mal mit Dichlormethan extrahiert. Die vereinigten organischen Phasen werden mit NaCI-Loesung gewaschen, ueber MgSO4 getrocknet, filtriert und dann das Loesungsmittel am Rotationsverdampfer entfernt. Das Rohprodukt wird entweder destilliert, umkristallisiert z.B. aus Hexan/Petrolether bzw. aus Hexan/Dichlormethan oder als Rohmischung in weiteren Reaktionen eingesetzt. Es entsteht ueblicherweise ein Gemisch aus Hydroxyestern und Lactonen in Verhaeltnissen von 99:1 bis 80:20 zugunsten des Hydroxyesters. Die vollstaendige Umwandlung in die entsprechenden Lactone (siehe Formel VII) erfolgt durch Ruehren des Gemisches mit 2 N NaOH-Loesung bei 60C fuer 1 h. Die Umsatz- und Enantiomeren-Analytik erfolgte gaschromatographisch unter Verwendung von Kapillarsaeulen der Firma IVA. 12-25 m Saeulen vom Typ IVADEX 1 (Saeule A), IVADEX 3 (Saeule B) und Hydrodex-beta-6-TBDM (Saeule C) kamen unter Verwendung von Helium als Traegergas auf einem HP 5890 II Gaschromatographen zum Einsatz. Die hier angefuehrten Umsaetze und Reaktionszeiten sind nicht optimiert, da zumeist in geschlossenen Gefaessen ohne Ableitung von CO2 gearbeitet wurde. t = 24 h, U = 95 %. S/C = 100, T = 30 C
  • 7
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  • [ 40255-48-9 ]
  • [ 201531-42-2 ]
  • 9
  • [ 292638-85-8 ]
  • pentacarbonyl<(N,N-dimethylamino)(p-bromophenyl)carbene>chromium(0) [ No CAS ]
  • [ 18469-37-9 ]
  • [ 30913-86-1 ]
  • [ 1122-91-4 ]
  • 10
  • [ 292638-85-8 ]
  • pentacarbonyl[(dimethylamino)(p-bromophenyl)carbene]chromium(0) [ No CAS ]
  • [ 30913-86-1 ]
  • 11
  • (Z)-4-(4-Bromo-phenyl)-4-(3-methyl-pyridin-2-ylamino)-but-3-enoic acid methyl ester [ No CAS ]
  • [ 30913-86-1 ]
  • 12
  • [ 67-56-1 ]
  • [ 20005-42-9 ]
  • [ 30913-86-1 ]
  • 13
  • [ 1122-91-4 ]
  • [ 292638-85-8 ]
  • [ 30913-86-1 ]
  • 14
  • [ 30913-86-1 ]
  • [ 1972-28-7 ]
  • C17H21BrN2O7 [ No CAS ]
  • C17H21BrN2O7 [ No CAS ]
  • 15
  • [ 1122-91-4 ]
  • 4-acetylbenzoyl-Rink resin [ No CAS ]
  • [ 30913-86-1 ]
  • 16
  • 4-bromobenzylidene-(3-methyl-pyridin-2-yl)-imine [ No CAS ]
  • [ 30913-86-1 ]
  • 17
  • [ 30913-86-1 ]
  • 5-(4-iodophenyl)-1-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}pyrrolidin-2-one [ No CAS ]
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  • [ 30913-86-1 ]
  • [ 128994-29-6 ]
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  • [ 30913-86-1 ]
  • [ 126135-43-1 ]
  • 24
  • [ 90766-44-2 ]
  • [ 30913-86-1 ]
  • 25
  • [ 851108-42-4 ]
  • [ 30913-86-1 ]
  • 26
  • [ 30913-86-1 ]
  • [ 509083-36-7 ]
YieldReaction ConditionsOperation in experiment
With lithium aluminium tetrahydride; In diethyl ether; at 0 - 20℃; for 6h;Heating / reflux; Preparation 3 1-(4-Bromophenyl)-butane-1,4-diol [0279] [CHEMMOL-00060] [0280] A solution of 4-(4-bromophenyl)-4-oxobutyric acid methyl ester (19 g, 70 mmol) (Preparation 2) in anhydrous diethyl ether (100 ml) was added dropwise to a suspension of LiAlH4 (5.3 g, 140 mmol) in ether (100 ml), while the temperature was kept below 5 C. with an ice bath. After 2 h at RT, the reaction mixture was refluxed for 4 h. It was then cooled to 5 C. and hydrolyzed with a saturated Na2SO4 solution with the temperature kept below 15 C. The suspension was filtered over celite and concentrated to yield a yellow oil (16.1 g) which was chromatographed over silica gel (eluent:DCM/MeOH 90/10) to yield 1-(4-bromophenyl)-butane-1,4-diol as an oil (15 g). 1H NMR (CDCl3): 7.40 (2H, d, J=8.4 Hz), 7.12 (2H, d, J=8.4 Hz), 4.65 (1H, br s), 4.50-4.60 (1H, m), 3.97 (1H, br s), 3.4-3.65 (2H, m), 1.6-1.85 (2H, m), 1.45-1.6 (2H, m).
  • 27
  • [ 5720-05-8 ]
  • [ 30913-86-1 ]
  • [ 497-19-8 ]
  • 4-(4'-Methyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
tetrakis(triphenylphosphine)palladium (0); In chloroform; toluene; Step (b) Preparation of 4-(4'-Methyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester To a stirred mixture of (4-methylphenyl)boronic acid (0.818 g, 0.00602 mol) and 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.3556 g, 0.00500 mol) in toluene (10 mL) was added tetrakis(triphenylphosphine)-palladium(0) (0.173 g, 0.000150 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol), and the mixture was heated at reflux under nitrogen for 12 hours and allowed to cool. The mixture was diluted with toluene and dichloromethane (10 mL/10 mL), and filtered through a pad of Celite. The Celite was washed with additional toluene and dichloromethane. Filtrate and washings were combined and washed with 2.0 M aqueous sodium carbonate, brine, 3% aqueous ammonium hydroxide, water, and brine. The organics were dried (Na2SO4) and rotary evaporated. The residue was dissolved in chloroform and purified by column chromatography on silica gel (144 g, 230-400 mesh), eluding with hexanes-acetone (6:1, 17*125 mL) to give 0.98 g of 4-(4'-methyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 121-122 C.
  • 28
  • [ 121-43-7 ]
  • [ 3972-65-4 ]
  • [ 30913-86-1 ]
  • [ 123324-71-0 ]
  • 4-(4'-tert-Butyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester [ No CAS ]
  • 4-(4'-tert-butyl-biphenyl-4-yl)-4-hydroxyimino-butyric acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; n-butyllithium;sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In tetrahydrofuran; diethyl ether; toluene; Step (a) Preparation of 4-(4'-tert-Butyl-biphenyl-4-yl)-4-oxo-butyric acid methyl ester To a stirred solution of 4-tert-butyl-bromobenzene (21.3 g, 0.0999 mol) in THF (30 mL) at -78 C. under nitrogen was added dropwise a 2.1 M solution of n-butyl lithium in hexanes (45 mL, 0.095 mol), and the mixture was stirred for 1.5 hours. To the mixture was added dropwise neat trimethylborate (10.2 mL, 0.090 mol), and the mixture was allowed to slowly warm to room temperature. The mixture was stirred overnight, then quenched by dropwise addition of 1.0 M aqueous hydrochloric acid. Brine was added, and the organic layer was dried (Na2SO4) and rotary evaporated. The residue was crystallized from n-heptane to give 4.65 g of crude 4-tert-butyl-phenyl-boronic acid as white needles. This material was used directly in the next reaction without further characterization. Thus, in a manner similar to Example 12, Step (b), 4-tert-butyl-phenyl-boronic acid (0.4287 g, 0.00241 mol) was allowed to react with 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (0.5443 g, 0.00200 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.0472 g, 0.0000408 mol) and 2.0 M aqueous sodium carbonate (2.4 mL, 0.0048 mol) in toluene (5 mL) to give, after chromatography on silica gel (270 g, 230-400 mesh), eluding with toluene then chloroform, 0.50 g. The material was dissolved in diethyl ether, washed with 0.10 M aqueous sodium hydroxide, water and brine. The organics were dried (K2CO3), and rotary evaporated to give 0.45 g of 4-(4'-tert-butyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 58-62 C.
  • 29
  • [ 5720-07-0 ]
  • [ 30913-86-1 ]
  • [ 54011-26-6 ]
YieldReaction ConditionsOperation in experiment
sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In toluene; Step (a) Preparation of 4-(4'-Methoxy-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester In a manner similar to Example 12, Step (b), (4-methoxyphenyl)boronic acid (0.913 g, 0.00601 mol) was allowed to react with 4-(4-bromo-phenyl)4-oxo-butyric acid, methyl ester (1.356 g, 0.00500 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.173 g, 0.000150 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol) in toluene (10 mL) to give, after chromatography on silica gel (270 g, 230-400 mesh), eluding with dichloromethane (15*250 mL); dichloromethane-methanol (100:1, 19*225 mL; 50:1, 5*225 mL), 1.386 g of 4-(4'-methoxy-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 96.0-100.5 C.
  • 30
  • [ 30913-86-1 ]
  • [ 128796-39-4 ]
  • 4-oxo-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid, methyl ester [ No CAS ]
  • 4-hydroxyimino-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid [ No CAS ]
YieldReaction ConditionsOperation in experiment
sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In toluene; Step (a) Preparation of 4-Oxo-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid, methyl ester In a manner similar to Example 12, Step (b), (4-trifluoromethyl-phenyl)boronic acid (1.285 g, 0.00676 mol) was allowed to react with 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.356 g, 0.00500 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.173 g, 0.000150 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol) in toluene (10 mL) to give, after chromatography on silica gel (270 g, 230-400 mesh), eluding with chloroform to give 1.42 g of 4-oxo-4-(4'-trifluoromethyl-biphenyl-4-yl)-butyric acid, methyl ester as a white solid; mp 140-142 C.
  • 31
  • [ 30913-86-1 ]
  • [ 151169-75-4 ]
  • 4-(3',4'-dichloro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In toluene; Step (a) Preparation of 4-(3',4'-Dichloro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester In a manner similar to Example 12, Step (b), (3,4-dichloro-phenyl)boronic acid (1.0569 g, 0.005539 mol) was allowed to react with 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.3636 g, 0.005019 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.1054 g, 0.0000912 mol) and 2.0 M aqueous sodium carbonate (5.5 mL, 0.011 mol) in toluene (11 mL) to give, after chromatography on silica gel (270 g, 230-400 mesh), eluding with hexanes-acetone (7:1) 1.432 g of 4-(3',4'-dichloro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 120-121 C.
  • 32
  • [ 108-86-1 ]
  • [ 1490-25-1 ]
  • [ 30913-86-1 ]
YieldReaction ConditionsOperation in experiment
aluminium trichloride; In dichloromethane; Step (a) Preparation of 4-(4-Bromo-phenyl)-4-oxo-butyric acid, methyl ester In a manner similar to Example 2, Step (a), bromobenzene (10.0 mL, 0.0950 mol) was allowed to react with 3-carbomethoxypropionyl chloride (12.9 mL, 0.105 mol) in the presence of aluminum chloride (26.9 g, 0.202 mol) in dichloromethane to give, after chromatography on silica gel (435 g, 230-400 mesh), eluding with hexanes-acetone (9:1, 10*400 mL; 8:1, 7*400 mL), 21.2 g of 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester as an off-white solid; mp 49-51 C.
  • 33
  • [ 768-35-4 ]
  • [ 30913-86-1 ]
  • 4-(3'-fluoro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In toluene; Step (a) Preparation of 4-(3'-Fluoro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester In a manner similar to Example 12, Step (b), (3-fluoro-phenyl)boronic acid (0.7698 g, 0.005502 mol) was allowed to react with 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.356 g, 0.00500 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.173 g, 0.000150 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol) in toluene (10 mL) to give, after chromatography on silica gel (270 g, 230-400 mesh), eluding with chloroform (18*125 mL), 1.221 g of 4-(3'-fluoro-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 99-101 C.
  • 34
  • tri-ortho-toluoylphosphine [ No CAS ]
  • [ 30913-86-1 ]
  • [ 126747-14-6 ]
  • 4-(4'-cyano-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
With triethylamine;palladium diacetate; In N-methyl-acetamide; A stirred mixture of (4-cyano-phenyl)boronic acid (0.220 g, 0.00150 mol), 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (0.2715 g, 0.00100 mol), triethylamine (0.418 mL, 0.0030 mol), tri(O-toluyl)phosphine (0.0191 g, 0.0000628 mol) and palladium(II)acetate (0.0067 g, 0.000030 mol) in dry dimethylformamide (4.0 mL) was heated at 105 C. under nitrogen for 2 hours and allowed to cool. For convenience, allowed to stand overnight. The mixture was diluted with diethyl ether, and the resulting suspension was filtered through Celite. The Celite and filtercake were washed with additional diethyl ether then dichloromethane. The filtrate and washings were combined and washed with 0.5 M aqueous hydrochloric acid, water, 3% aqueous ammonium hydroxide, water, and brine. The organics were dried (Na2SO4) and rotary evaporated. The residue was dissolved (chloroform) and chromatographed on silica gel (35 g, 230-400 mesh), eluding with hexanes-acetone (4:1, 30*30 mL) to give 0.172 g of 4-(4'-cyano-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a pale yellow solid; mp 149-151 C.
  • 35
  • [ 30913-86-1 ]
  • [ 128312-11-8 ]
  • 4-(4'-methylsulfanyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester [ No CAS ]
YieldReaction ConditionsOperation in experiment
sodium carbonate; tetrakis(triphenylphosphine)palladium (0); In toluene; Step (a) Preparation of 4-(4'-Methylsulfanyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester In a manner similar to Example 12, Step (b), 4-(methylsulfanyl-phenyl)boronic acid (0.930 g, 0.00553 mol) was allowed to react with 4-(4-bromo-phenyl)-4-oxo-butyric acid, methyl ester (1.356 g, 0.00500 mol) in the presence of tetrakis(triphenylphosphine)palladium(0) (0.162 g, 0.000140 mol) and 2.0 M aqueous sodium carbonate (5.0 mL, 0.010 mol) in toluene (10 mL) to give, after chromatography on silica gel (168 g, 230-400 mesh), eluding with hexanes-acetone (11:1, 20*125 mL; 9:1, 10*125 mL; 6:1, 30*125 mL), 0.405 g of 4-(4'-methylsulfanyl-biphenyl-4-yl)-4-oxo-butyric acid, methyl ester as a white solid; mp 137-140 C.
 

Historical Records

Technical Information

• Acyl Group Substitution • Alkyl Halide Occurrence • Baeyer-Villiger Oxidation • Barbier Coupling Reaction • Baylis-Hillman Reaction • Benzylic Oxidation • Birch Reduction • Blanc Chloromethylation • Bouveault-Blanc Reduction • Bucherer-Bergs Reaction • Catalytic Hydrogenation • Clemmensen Reduction • Complex Metal Hydride Reductions • Corey-Bakshi-Shibata (CBS) Reduction • Corey-Chaykovsky Reaction • Ester Cleavage • Fischer Indole Synthesis • Friedel-Crafts Reaction • General Reactivity • Grignard Reaction • Henry Nitroaldol Reaction • Hiyama Cross-Coupling Reaction • Horner-Wadsworth-Emmons Reaction • Hydride Reductions • Hydrogenolysis of Benzyl Ether • Kinetics of Alkyl Halides • Kumada Cross-Coupling Reaction • Lawesson's Reagent • Leuckart-Wallach Reaction • McMurry Coupling • Meerwein-Ponndorf-Verley Reduction • Passerini Reaction • Paternò-Büchi Reaction • Petasis Reaction • Peterson Olefination • Pictet-Spengler Tetrahydroisoquinoline Synthesis • Preparation of Aldehydes and Ketones • Preparation of Alkylbenzene • Preparation of Amines • Prins Reaction • Reactions of Aldehydes and Ketones • Reactions of Alkyl Halides with Reducing Metals • Reactions of Amines • Reactions of Benzene and Substituted Benzenes • Reactions of Dihalides • Reactions with Organometallic Reagents • Reformatsky Reaction • Robinson Annulation • Schlosser Modification of the Wittig Reaction • Schmidt Reaction • Specialized Acylation Reagents-Carbodiimides and Related Reagents • Specialized Acylation Reagents-Ketenes • Stille Coupling • Stobbe Condensation • Substitution and Elimination Reactions of Alkyl Halides • Suzuki Coupling • Tebbe Olefination • Ugi Reaction • Vilsmeier-Haack Reaction • Wittig Reaction • Wolff-Kishner Reduction

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