Structure of 14814-17-6
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CAS No. : | 14814-17-6 |
Formula : | C15H14O3 |
M.W : | 242.27 |
SMILES Code : | O=C(C1=CC=C(OCCO)C=C1)C2=CC=CC=C2 |
MDL No. : | MFCD00623913 |
InChI Key : | PNTLMFABGCHLMN-UHFFFAOYSA-N |
Pubchem ID : | 3090643 |
GHS Pictogram: |
![]() |
Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
Num. heavy atoms | 18 |
Num. arom. heavy atoms | 12 |
Fraction Csp3 | 0.13 |
Num. rotatable bonds | 5 |
Num. H-bond acceptors | 3.0 |
Num. H-bond donors | 1.0 |
Molar Refractivity | 68.78 |
TPSA ? Topological Polar Surface Area: Calculated from |
46.53 Ų |
Log Po/w (iLOGP)? iLOGP: in-house physics-based method implemented from |
2.47 |
Log Po/w (XLOGP3)? XLOGP3: Atomistic and knowledge-based method calculated by |
2.5 |
Log Po/w (WLOGP)? WLOGP: Atomistic method implemented from |
2.29 |
Log Po/w (MLOGP)? MLOGP: Topological method implemented from |
1.98 |
Log Po/w (SILICOS-IT)? SILICOS-IT: Hybrid fragmental/topological method calculated by |
3.16 |
Consensus Log Po/w? Consensus Log Po/w: Average of all five predictions |
2.48 |
Log S (ESOL):? ESOL: Topological method implemented from |
-3.08 |
Solubility | 0.201 mg/ml ; 0.000831 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (Ali)? Ali: Topological method implemented from |
-3.12 |
Solubility | 0.183 mg/ml ; 0.000754 mol/l |
Class? Solubility class: Log S scale |
Soluble |
Log S (SILICOS-IT)? SILICOS-IT: Fragmental method calculated by |
-4.84 |
Solubility | 0.00347 mg/ml ; 0.0000143 mol/l |
Class? Solubility class: Log S scale |
Moderately soluble |
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) |
No |
CYP1A2 inhibitor? Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set) |
Yes |
CYP2C19 inhibitor? Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set) |
Yes |
CYP2C9 inhibitor? Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set) |
No |
CYP2D6 inhibitor? Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set) |
No |
CYP3A4 inhibitor? Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set) |
No |
Log Kp (skin permeation)? Skin permeation: QSPR model implemented from |
-6.0 cm/s |
Lipinski? Lipinski (Pfizer) filter: implemented from |
0.0 |
Ghose? Ghose filter: implemented from |
None |
Veber? Veber (GSK) filter: implemented from |
0.0 |
Egan? Egan (Pharmacia) filter: implemented from |
0.0 |
Muegge? Muegge (Bayer) filter: implemented from |
0.0 |
Bioavailability Score? Abbott Bioavailability Score: Probability of F > 10% in rat |
0.55 |
PAINS? Pan Assay Interference Structures: implemented from |
0.0 alert |
Brenk? Structural Alert: implemented from |
0.0 alert: heavy_metal |
Leadlikeness? Leadlikeness: implemented from |
No; 1 violation:MW<1.0 |
Synthetic accessibility? Synthetic accessibility score: from 1 (very easy) to 10 (very difficult) |
1.74 |
* 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 |
---|---|---|
21% | With potassium carbonate; sodium iodide; In acetone;Heating / reflux; | Step 1: {4-[(2-Hydroxyethyl)oxy]phenyl}(phenyl)methanone (5)To a solution of 4-hydroxybenzophenone (6.0 g, 29.7 mmol) in acetone (50 mL) were added K2CO3 (12.3 g, 89.0 mmol) and 2-chloroethanol (4.0 mL, 59.3 mmol), followed by addition of NaI (4.50 g, 29.7 mmol). The reaction mixture was refluxed under nitrogen overnight. The mixture was cooled to room temperature. The white solid was filtered off and washed with acetone (100 mL). The filtrate was concentrated to a brown oil residue with some white solid. EtOAc (200 mL) was added, the white solid was filtered off and then washed with 50 mL of EtOAc. The filtrate was washed with 1 N NaOH, water, brine and dried over Na2SO4. Concentration afforded a pale yellow oil which was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 60% EtOAc:hexanes to give 5 as a white solid (1.52 g, 21%). 1H NMR (400 MHz, CDCl3): delta 4.00-4.05 (m, 2H), 4.15-4.20 (m, 2H), 6.98 (d, J=8.7 Hz, 2H), 7.45-7.50 (m, 2H), 7.55-7.60 (m, 1H), 7.75 (d, J=7.1 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H). |
Preparation of Compound I; Synthesis of 3-(2-methylaziridin-l-yl)propionic acid 2-(4-benzoylphenoxy)ethyl ester (AZBP); To a 250 mL, one -neck, round bottom flask equipped with a magnetic stirrer were added sodium hydroxide (10.0 g, 0.250 mol) in a water (45 mL)/ethanol (20 mL) solution and 4-hydroxybenzophenone (Alfa Aesar, 50.0 g, 0.250 mol) and the mixture was heated to 55 0C. Chloroethanol (Aldrich, 20.3 g, 0.250 mol) in ethanol (25 mL) was then added dropwise to the reaction flask and the mixture heated to 75 0C for 8 hours then cooled to room temperature. The precipitate was collected by filtration, washed with water and recrystallized three times from ethanol/water to obtain 24.4 g of a white solid (4-(2- hydroxyethoxy)benzophenone). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; water; | (b) 43 g (0.15 mole) of 4-(2-acetoxyethoxy)-benzophenone are dissolved in 60 ml of ethanol and boiled with 17 ml of 32% strength sodium hydroxide solution under reflux, with stirring, for 20 minutes. After cooling, the reaction mixture is neutralized with hydrochloric acid, whereupon the end product is precipitated as a white solid. The reaction mixture is poured into 500 ml of water, and the solid is filtered off with suction, washed and dried in vacuo at 50 C. for 5 hours. This gives 35 g (95%) of 4-(2-hydroxyethoxy)-benzophenone, melting point 82 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
from 2-(p-benzoylphenoxy)-ethanol and ethyl isocyanate there is obtained [2-(p-benzoylphenoxy)-ethyl]N-ethylcarbamate, m.p. 87-90 C.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium iodide; In toluene; at 60℃; for 1.5h;Reflux; | 4-hydroxybenzophenone (262 g, 1.32 mol)NaI (6.5 g, 0.043 mol),Ethylene carbonate (125 g, 1.42 mol) andToluene (10 mL) were added to a 2000 mL three-necked flask,Raise the temperature until the system is clear.Continue to raise the temperature to the reaction system was refluxed for 1.5h,After the TLC test reaction is completed, the heating is stopped,Cooled to 60 C.To the reaction system was added water and ethyl acetate,extraction,The organic phase was dried over anhydrous sodium sulfate,Concentrated to give 304 g of a pale yellow solid,Yield 95%. |
94% | With sodium iodide; In toluene; at 99 - 176℃; for 0.5h;Product distribution / selectivity; | A mixture of ethylene carbonate (124.6 g; 1.07 eq.), sodium iodide (6.3 g; 0.03 eq.), 4-hydroxybenzophenone (262 g; 1 eq.) and toluene (8.1 g) was heated. At99C a clear solution was obtained. The reaction mixture was heated with reflux condenser to 176C over one hour, during which gas evolution occurred. After an additional ½ hour at 176C, the reaction mixture was cooled to 122C and toluene (350 g) and water (24 g) was added. The lower phase was cut and discarded. More water (14 g) was added and the lower phase was again cut and discarded. Water and toluene (95 g in total) was azeotropically removed, reaching a boiling point of 11 1 C. More toluene (1 14 g) was added and the product was isolated by filtration at 8C. In total, 302 g of 4-(2-hydroxyethoxy)benzophenone (94%) was obtained after drying as white crystals (99.8 % chromatographic purity). |
from 4-hydroxy-benzophenone and ethylene carbonate there is obtained 2-(p-benzoylphenoxy)-ethanol, m.p. 78-80 C.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With titanium tetrachloride; zinc; In tetrahydrofuran; at 20℃; for 5h;Heating / reflux; | Step 2: 2-({4-[Phenyl(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}oxy)ethanol (6)To a stirred suspension of Zn (0.65 g, 9.91 mmol) in THF (10 mL) was added TiCl4 (0.55 mL, 4.95 mmol) dropwise. The mixture was refluxed under nitrogen for 2.5 h. After cooling to room temperature, a solution of 5 (0.30 g, 1.24 mmol) and 3,3,5,5-tetramethylcyclohexanone (0.59 g, 3.71 mmol) in THF (17 mL) was added at once. The reaction mixture was refluxed for another 2.5 h. Following cooling to room temperature, the reaction was quenched with 10% K2CO3 (40 mL). The quenched reaction mixture was filtered through a pad of celite and the pad was washed with EtOAc (100 mL). The filtrate was transferred to a separatory funnel, the layers were separated, and the aqueous layer was extracted with EtOAc (50 mL). The organic extracts were combined, washed with brine, dried (Na2SO4) and concentrated to give a pale yellow oil. The residue was further purified by chromatography on a silica gel column eluted with a gradient from hexanes to 20% EtOAc:hexanes to give 6 as a white solid (0.35 g, 78%). mp 131-132 C. 1H NMR (400 MHz, CD3OD): delta 0.91 (s, 6H), 0.92 (s, 6H), 1.29 (s, 2H), 1.95 (s, 2H), 1.99 (s, 2H), 3.80-3.85 (m, 2H), 4.00-4.05 (m, 2H), 6.85 (d, J=8.8 Hz, 2H), 7.06 (d, J=8.6 Hz, 2H), 7.10-7.20 (m, 3H), 7.20-7.25 (m, 2H). LRMS (ESI): m/z 365 (M+H)+. Anal. Calcd for C25H32O2: C, 82.37; H, 8.85. Found: C, 82.11; H, 9.03. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With triethylamine; In hexane; ethyl acetate; butanone; at -10 - 20℃; for 16.5h; | Synthesis of 2-propenoic acid 2-(4-benzoylphenoxy)ethyl ester (INI-7) 3.6 g (15 mmol) <strong>[14814-17-6]4-(2-hydroxyethoxy)benzophenone</strong> and 1.8 g (18 mmol) triethyl amine were dissolved in 40 ml 2-butanone. The mixture was cooled to -10C and 2.3 g (18 mmol) 3-chloro-propionyl chloride was added drop wise while the temperature was kept below -5C. The reaction was allowed to continue first at 0C for 30 minutes, followed by 16 hours at room temperature. The precipitated salts were removed by filtration and the solvent was removed under reduced pressure. The crude 3-chloro-propionic acid 2-(4-benzoylphenoxy)ethyl ester was purified by preparative column chromatography on a Prochrom LC80 column, using n.-hexane/ethyl acetate 70/30 as eluent at a flow rate of 50 ml/min and Kromasil 60A 10 micron as silica. 1.9 g (32 %) of 3-chloro-propionic acid 2-(4-benzoylphenoxy)ethyl ester was isolated. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
I b) Copolymerizable Photoinitiators, General Production Instructions; 1 mol of isocyanate as given in Table 1 was dissolved in anhydrous tetrahydrofuran (THF) at from 20 to 25 C. (ambient temperature) such that the urethane adduct produced in the first reaction step subsequently existed as a 35 wt % strength solution. After covering with dry nitrogen, 1 mol of hydroxyethyl acrylate, previously stabilized with 100 ppm of Tempol, was then added within a period of 5 minutes at room temperature. 500 ppm by weight (based on isocyanate used) of dibutyltin dilaurate were then added, and the mixture was stirred for approximately 5 hours at 50 C. while the fall in isocyanate content was monitored titrimetrically. Once the theoretical isocyanate content of the monourethane had been achieved, the molar amount of ethylene glycol p-benzophenone ether groups corresponding to the isocyanate still free is added as a 35 wt % strength solution from stage Ia) in THF having a temperature of 50 C. The reaction mixture was then further stirred at 50 C. until no more isocyanate groups could be detected titrimetrically. The resulting reaction mixtures were used directly in the following polymerization reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | I a) Ethylene glycol p-benzophenone ether; In a laboratory autoclave having a capacity of 2 L there were placed 520 g of diethylene glycol diethyl ether, 286 g of p-hydroxybenzophenone (>98 wt %), and 0.8 g of powdered potassium hydroxide. A pressure test was then carried out for 30 minutes using dry nitrogen. Following pressure let-down to atmospheric pressure and heating of the reaction mixture under a blanket of nitrogen to 120 C., 95.4 g of ethylene oxide were continuously forced in to give a maximum internal pressure of 4 bar over a period of 1 h. On completion of gassing with ethylene oxide, the reaction mixture was allowed to react, until the pressure remained constant for at least 30 minutes. The reaction mixture was discharged from the autoclave in the hot state, neutralized with 5 wt % strength aqueous hydrochloric acid, and poured into 2 L of ice water, and the reaction product was caused to crystallize by constant agitation. The resulting solid matter was filtered off in vacuo, washed with ice water and dried in vacuo (40 C., 10 mbar absolute). The resulting filtrate was concentrated in a rotary film evaporator to 20% of its volume, the precipitated product filtered off in vacuo, washed with ice water and likewise dried in vacuo. The total yield was 82% of theory. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; triethylamine; In ethanol; dichloromethane; water; | Synthesis of 3-(2-methylaziridin-1-yl)propionic acid 2-(4-benzoylphenoxy)ethyl ester (AZBP) To a 250 mL, one-neck, round bottom flask equipped with a magnetic stirrer were added sodium hydroxide (10.0 g, 0.250 mol) in a water (45 mL)/ethanol (20 mL) solution and 4-hydroxybenzophenone (Alfa Aesar, 50.0 g, 0.250 mol) and the mixture was heated to 55 C. Chloroethanol (Aldrich, 20.3 g, 0.250 mol) in ethanol (25 mL) was then added dropwise to the reaction flask and the mixture heated to 75 C. for 8 hours then cooled to room temperature. The precipitate was collected by filtration, washed with water and recrystallized three times from ethanol/water to obtain 24.4 g of a white solid (<strong>[14814-17-6]4-(2-hydroxyethoxy)benzophenone</strong>). To a 200 mL, one neck, round bottom flask equipped with a magnetic stirrer were added <strong>[14814-17-6]4-(2-hydroxyethoxy)benzophenone</strong> (12.1 g, 5.00 mmol), triethylamine (7.7 mL, 5.57 g, 5.50 mmol), and methylene chloride (60 mL) and the mixture cooled to 0 C. Acryloyl chloride (Aldrich, 4.3 ml, 0.48 g, 5.3 mmol) in 40 mL CH2Cl2 solution was added over 30 minutes and then the mixture was stirred at room temperature for one hour followed by addition of 50 mL of water. The organic phase was washed 2* with water, dried over MgSO4, filtered and concentrated under vacuum to give 14.8 g of a pale yellow solid (acrylic acid 2-(4-benzoylphenoxy)ethyl ester). To a 100 mL, one-neck, round bottom flask equipped with a magnetic stirrer were added starting material acrylic acid 2-(4-benzoylphenoxy)ethyl ester (14.75 g, 49.78 mmol), 2-methylaziridine (3.45 g, 54.4 mmol) and methylene chloride (10 mL). The reaction mixture was stirred at ambient temperature overnight. The reaction mixture was then concentrated under reduced pressure for 30 minutes to obtain 17.4 g of Compound I as a viscous light orange oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 0 - 20℃; for 1.5h; | To a 200 mL, one neck, round bottom flask equipped with a magnetic stirrer were added <strong>[14814-17-6]4-(2-hydroxyethoxy)benzophenone</strong> (12.1 g, 5.00 mmol), triethylamine (7.7 mL,5.57 g, 5.50 mmol), and methylene chloride (60 mL) and the mixture cooled to 0 0C. Acryloyl chloride (Aldrich, 4.3 ml, 0.48 g, 5.3 mmol) in 40 mL CH2Cl2 solution was added over 30 minutes and then the mixture was stirred at room temperature for one hour followed by addition of 50 mL of water. The organic phase was washed 2X with water, dried over MgSO4, filtered and concentrated under vacuum to give 14.8 g of a pale yellow solid (acrylic acid 2-(4-benzoylphenoxy)ethyl ester). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With titanium tetrachloride; zinc; In 2-methyltetrahydrofuran; at 15 - 50℃;Product distribution / selectivity; | Hydroxyethoxybenzophenone (67.66g, 279.3 mmol, 1 eq), 3- chloropropiophenone (47.24 g, 279.3 mmol, 1 eq), zinc powder (69.45 g, 1062 mmol, 3.8 eq) and 2-methyltetrahydrofuran (895 g, 1041 ml) were charged to the reactor. The slurry was degassed and the vessel was filled with nitrogen gas. The slurry was cooled to <15C and then titanium tetrachloride (101.5 g, 535.1 mmol, 1.92 eq.) was slowly dosed maintaining a temperature below 20C. The slurry was heated to 50C and the temperature was maintained for 15 minutes. The slurry was heated to 70C and the pressure was reduced and 2- methyltetrahydrofuran (403 g) was distilled off at 70C and 650 mbar over 1 hour. Zinc(s) was filtered off and the filter was rinsed with 2-methyltetrahydrofuran (64 g). The pressure was reduced to 200 mbar and 2-methyltetrahydrofuran (344 g) was distilled off at 43-53C and 200-160 mbar pressure (total amount of pure 2- methyltetrahydrofuran recycled is 76%). Toluene (151g) was charged. A mixture of hydrochloric acid (aq) (116 g, 37 %) and water (281 g) was added maintaining a temperature below 20C. The lower aqueous phase was cut (at 30C) and discarded. Water (128 g) was added. The lower aqueous phase was cut (at 55C) and discarded. Water (131 g) was added again and the lower aqueous phase was cut again (at 55C) and discarded. The pressure was reduced and 2- methyltetrahydrofuran + toluene + water was distilled off at 150-50 bar and 37- 60C until there was a residual volume of about 130 ml. Before the crystallisation/precipitation process, the ratio of Z:E isomers of Ospemifene was about 5.5:1. Then, methanol (125 g) was charged and the solution was filtered. To the filtrate was added methanol to a total weight of 572 g (content estimated to 121 g raw product + toluene and 451 g methanol). Water (148 g) was added to the filtrate and the solution was heated to 50C. The solution was then cooled to 48C and seeded. The mixture was slowly cooled to 15C over 5 hours and maintained at this temperature overnight. The product was isolated by filtration and the filter cake was rinsed with methanol(aq) (74%, 141 g). Yield 50.4 g after drying (47.6%). Purity >99% by HPLC (standard). The raw product contained 98.81 % Z-isomer, 0.61% E-isomer (hence a Z:£ ratio of 162:1 ) and 0.58% of other products. The product obtained (in a yield of 96%; hence, advantageously yield is not significantly decreased) after recrystallisation was 99.9% Z-isomer, 0.05% E-isomer (hence a Z:E ratio of 1991 : 1 ) and 0.05% of other products. Hence, an extremely pure and selective Z-isomer of the compound of formula I is obtained by this method of the invention. |
With titanium tetrachloride; zinc; In 2-methyltetrahydrofuran; at -10 - 80℃; for 5.5h;Inert atmosphere; | Zn powder (172 g, 2.6 mol) was added to the 3 L reaction flask, respectively2-methyltetrahydrofuran (1800 mL),Stir well and cool to -10 C,Nitrile was slowly added, TiCl4 (250 g, 1.32 mol) was slowly added dropwise,Add to warm up to room temperature for 30min,And then heated to 80 C for 2 h.Cooling to 40 ,A solution of 2- (4-benzophenoxy) -1-ethanol (108 g, 0.45 mol) was added dropwise3-chlorophenylacetone (76 g, 0.45 mol)2-methyltetrahydrofuran solution (800 ml).Plus heating temperature to 80 under the reaction 3h,After TLC detection reaction is completed,React and cool the system temperature to room temperature |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; at 90℃; for 24h; | 4-hydroxy benzophenone (9.9 g, 50 mmol), 2-bro-moethanol (7.5 g, 60 mmol) and potassium carbonate (10 g, 75 mmol) were added to N,N-dimethylformamide (DMF, 150 mE), and stirred at 90 C. for one day. A solvent was distilled off, and dichioromethane was added. The mixture extracted with water and saturated saline solution, and dried. A solvent was distilled off to obtain a pale yellow powder (crude yield 12 g). This compound was used in the next reaction. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With triethylamine; In dichloromethane; at 0 - 23℃; | (4-(2-Hydroxyethoxy) phenyl (phenyl) methanone ( 5 g, 20.64 mmol ) was dissolved in DCM (50 ml) and the solution was cooled on ice-bath to 0-5 C. Triethylamine (5.75 ml, 41.3 mmol) was added followed by benzoyl chloride (2.87 ml, 24.77 mmol) maintaining the temperature below 5 C. After the additions the cooling bath was removed and the mixture was stirred at room temperature for 2 h. Reaction was quenched by addition of 5 % HCl-solution (25 ml) and the phases were separated. Organic phase was washed with water (25 ml), saturated NaHC03- solution (2 x 25 ml), water (25 ml) and brine (25 ml). After drying (Na2S04) and filtration the solution was concentrated in vacuo. The solid residue was re- crystallized from MeOH yielding the title compound as a white solid (5.52 g, 15.94 mmol, 77 ). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With triethylamine; In dichloromethane; at 0 - 23℃; | (4-(2-Hydroxyethoxy)phenyl)(phenyl)methanone (15 g, 61.9 mmol) was .dissolved in dichloromethane (200 ml) and cooled on ice-bath to 0-5 Triethylamirie (17.26 ml, 124 mmol) was added followed by pivaloyl chloride (8.39 mlj 68.1 mmol) maintaining the temperature below 5 C. After the additions the cooling bath was removed and the mixture was stirred at room temperature (23 C) for 12 hours. Reaction was quenched by addition of 5 % HCl-solution (150 ml) and the phases were separated. Organic phase was washed with 1 % NaOH-solution (2 x 50 ml), water (100 ml) and brine (100 ml). After drying with Na2S04 the solution was filtered through a small pad of silica and concentrated in vacuo. The title compound was obtained as a yellow solid (20.1 g, 61.6 mmol, 99 '). 1H-NMR (400 MHz, CDC13) (ppm): 7.83 (2H, d, 7=8,8Hz, ArH), 7.76 (2Eta, m, ArH), 7.57 (1Eta, tt, 7=7.2 Hz, 7= 1.2Hz, ArH), 7.47 (2Eta, t, 7=7, 6Hz, ArH), 6.98 (2Eta, d, 7=9.2Hz, ArH), 4.45 (2Eta, t, 7=4.8Hz, CH2CH2OPiv), 4.26 (2Eta, t, 7=5.2Hz, ArOCH2CH2), 1.21 (9H, s, 3 x Me). 13C-NMR (100 MHz, CDC13) delta (ppm): 195.8, 178.8, 162.6, 138.6, 133.0, 132.4, 130.9, 130.1 , 128.6, 1 14.6, 66.5, 62.8, 39.2, 27,5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
54% | With toluene-4-sulfonic acid; In toluene; for 7h;Reflux; | A. mixture of (4-(2-hydrpxyethoxy) phenyl (phenyl), methanone (15.g, 61.9 mmol), benzoic acid (8.32 g, 68.1 mmol) and p-TsOH , .(1.18 g, 6.19 mmol) were stirred under reflux in toluene (100 ml) with simultaneous water removal for 7 h. After cooling at room temperature the reaction was quenched by addition of saturated NaHCO3-solution,(50 ml). The phases were separated and toluene phase was washed with saturated NaHC03-solution (50 ml), water (50 ml) and saturated . NaCl-solution (50 ml). After drying (Na2S04) and filtration the solution was concentrated in vacuo. The oily residue was dissolved DCM and filtered through a small pad of silica and concentrated. The title compound was obtained as a white solid (1 1.58 g, 33.4 mmol, 54 %). 1H-NMR (400 MHz, CDC1 ) (ppm): 8.06 (2H, dd, 7 = 7-2 Hz, J = 1.2 Hz,.ArH), 7.84 (2Eta, d, J = 8.8 Hz, ArH), 7.75 (2Eta, dd, J = 8.4 Hz, J - 1.6 Hz, ArH), 7.57 (2Eta, td, J = 8.0 Hz, J = 1.6 Hz, ArH), 7.49-7.43 (4Eta, m, ArH), 7.02 (2Eta, d, J = 8.8 Hz, ArH), 4.71 (2H, t, J = 5.2 Hz, CH2CH2OBz), 4.40 (2Eta, t, J = 4.8 Hz, ArOCH2CH2). 13C-NMR (100 MHz, CDC13) delta (ppm): 195.6,' 166.6, 162.2, 138.3, 133.3, 132.7, 132.1 , 130.7, 129.8, 128.5, 128.3, 114.3, 66.3, 63.2. |
A200487 [611-94-9]
(4-Methoxyphenyl)(phenyl)methanone
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