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CAS No. : | 5669-19-2 | MDL No. : | MFCD00854174 |
Formula : | C10H10O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | RYNDYESLUKWOEE-UHFFFAOYSA-N |
M.W : | 162.19 | Pubchem ID : | 303571 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.1 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 47.13 |
TPSA : | 37.3 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.65 cm/s |
Log Po/w (iLOGP) : | 1.64 |
Log Po/w (XLOGP3) : | 2.31 |
Log Po/w (WLOGP) : | 1.87 |
Log Po/w (MLOGP) : | 2.2 |
Log Po/w (SILICOS-IT) : | 2.07 |
Consensus Log Po/w : | 2.02 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.56 |
Log S (ESOL) : | -2.47 |
Solubility : | 0.546 mg/ml ; 0.00337 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.73 |
Solubility : | 0.301 mg/ml ; 0.00186 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.61 |
Solubility : | 0.397 mg/ml ; 0.00245 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.38 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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 |
---|---|---|
23.8 g | at 30 - 60℃; | 16.2 g of 2-benzylacrylic acid and 12.3 ml of thioacetic acid were were charged into a clean and dry R.B.flask and stirred at about 30°C for about 1 hour. The reaction mixture was heated to about 60°C and stirred for about 4 hours.The excess of thioacetic acid was distilled off completely to afford the title compound as residue. Yield: 23.8 g |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With thionyl chloride; at 0 - 20℃; for 18h; | A solution of benzylmalonic acid (20.0 g, 0.103 mol, 1 eq) and paraformaldehyde (4.94 g, 0.164 mol, 1.6 eq) in ethyl acetate (150 mL) was cooled (0 C.) and treated with diethylamine (10.65 mL, 0.103 mol, 1 eq) drop wise, keeping the reaction temperature below 20 C. The reaction was then warmed to reflux for 90 minutes and cooled again on ice. The homogeneous solution was treated with water (20 mL) and concentrated aqueous HCl (12N) (9.0 mL, 0.108 mol) drop wise, keeping the reaction temperature below 10 C. The phases were then separated. The organic layer was washed with brine (100 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum giving 2-methylene-3-phenylpropanoic acid (10) as a white solid (15 g, 90%). A solution of 10 (10.3 g, 63.5 mmol) in methanol (100 mL) was cooled on ice and treated dropwise with thionyl chloride (14.0 mL, 192 mmol). After warming to ambient temperature, the reaction was stirred for 18 hours at room temperature and concentrated in vacuo. The crude product was dissolved in diethyl ether, washed with a saturated aqueous solution of sodium bicarbonate and brine, dried over sodium sulfate, filtered, and the filtrate concentrated in vacuo providing the methyl ester 11 (11.2 g, 100%) as a pale yellow oil. To a solution of (+/-)2 (2 g, 8.643 mmol, 1 eq), 2-benzyl-acrylic methyl ester 11 (3.19 g, 0.0182 mol, 2.1 eq) in methanol (25 mL) was added triethylamine (3.54 mL, 25.93 mmol, 3 eq) and the solution was heated to reflux for 16 hours under argon. The reaction mixture was concentrated in vacuo, then dissolved in ethyl acetate (200 mL). The mixture was extracted with a 1N aqueous solution of hydrochloric acid (2×200 mL). The combined aqueous phase was alkalinized to pH 8 with solid sodium hydrogenocarbonate, then extracted with ethyl acetate (3×150 mL). The combined organic extracts were dried (sodium sulfate), filtered and concentrated in vacuo to afford a clear tan oil. This oil was purified by column chromatography (eluent:dichloromethane/methanol=98:2) affording the desired compound 12 (mixture of diastereoisomers) (1.07 g, 30.5%). To a stirred solution of 12 (0.265 g, 0.650 mmol, 1 eq) in anhydrous dichloromethane (3 mL) was added triethylamine (154 muL, 11.05 mmol, 1.7 eq), followed by drop wise addition of a solution of N-phenyltrifluoromethanesulfonimide (0.347 g, 0.975 mmol, 1.5 eq) in anhydrous dichloromethane (0.5 mL) at room temperature under argon. The reaction mixture was allowed to stir for 1 h at room temperature. Dichloromethane (20 mL) was added to the mixture, which was washed with a IN aqueous solution of sodium hydroxide (20 mL) and brine (20 mL). The organic layer was then dried (sodium sulfate), filtered, and concentrated in vacuo. The crude product was purified by column chromatography (eluent:dichloromethane) affording the desired compound 13 (mixture of diastereoisomers) (0.281 g, 80%). A mixture of triflate 13 (0.500 g, 0.927 mmol, 1 eq), diphenylphosphinoferrocene (DPPF) (77 mg, 15 mol %, 0.139 mmol), Pd2(dba)3 (42.5 mg, 5 mol %), sodium tert-butoxide (0.196 g, 2.04 mmol, 2.2 eq) and benzophenone imine (187 muL, 1.112 mmol, 1.2 eq) in anhydrous toluene (40 mL) was degassed using vacuum and argon. The mixture was then heated to 80 C. for 16 hours. The reaction mixture was cooled to room temperature and quenched by addition of an aqueous saturated solution of ammonium chloride (100 mL). The organic layer was separated. The aqueous layer was further extracted with dichloromethane (2×100 mL) and the combined organic extracts were washed with brine (100 mL) prior to drying with sodium sulfate, filtering, and concentration in vacuo. The crude imine 14 was used for the next step without further purification (0.460 g, 85%). A mixture of the crude imine 14 (0.4 g, 0.682 mmol, 1 eq), hydroxylamine hydrochloride (96.5 mg, 1.365 mmol, 2 eq), sodium acetate (282 mg, 3.425 mmol, 5 eq) in methanol (10 mL) was stirred at room temperature for 45 minutes. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane (3×50 mL) and water (50 mL). The combined organic extracts were washed with brine (50 mL) and dried over sodium sulfate. The organic extracts were filtered and concentrated in vacuo. The crude product was purified by column chromatography (eluent:dichloromethane/methanol=99:1) affording the desired compound 15 (mixture of diastereoisomers) (0.295g, 100%). To a cooled (0 C.), stirred solution of the aniline derivative 15 (0.200 g, 0.492 mmol, 1 eq) and triethylamine (135muL, 0.983 mmol, 2eq) in anhydrous dichloromethane (10 mL) was added drop wise acetyl chloride (55 muL, 0.738 mmol, 1.5 eq). The mixture was stirred for 1 hour at room temperature and washed with an aqueous saturated solution of sodium hydrogenocarbonate. The aqueous layer was further extracted with dichloromethane (2×25 mL). The combined organic extracts were washed with brine (50 mL), then dried (sodium sulfate) prior to filtration and conc... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | (b) 2-(R,S)-Benzyl-3-benzyloxyamino-propionic Acid A mixture of 2-benzyl-acrylic acid (8.0 g, 55 mmol) and O-benzylhydroxylamine (16.0 g, 130 mmol) was heated at 80 C. for 18 hours. The reaction mixture was cooled, diluted with diethyl ether (100 mL) and extracted with 1M sodium carbonate (3*100 mL). The combined aqueous extracts were acidified with 3M citric acid and then re-extracted with dichloromethane (3*100 mL). The combined organic extracts were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to yield 2-(R,S)-benzyl-3-benzyloxyamino-propionic acid as a white crystalline solid (7.82 g, 53%). 1H-NMR; δ (CDCl3), 7.61-7.15 (10H, m), 4.66 (2H, d, J=1.7 Hz), 3.13-2.94 (4H, m), 2.84-2.74 (1H, m). | |
53% | Step B 2-(R,S)-Benzyl-3-benzyloxyamino-propionic Acid A mixture of 2-benzyl-acrylic acid (8.0 g, 55 mmol) and O-benzylhydroxylamine (16.0 g, 130 mmol) was heated at 80 C. for 18 hours. The reaction mixture was cooled, diluted with diethyl ether (100 mL) and extracted with 1 M sodium carbonate (3*100 mL). The combined aqueous extracts were acidified with 3 M citric acid and then re-extracted with DCM (3*100 mL). The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 2-(R,S)-benzyl-3-benzyloxyamino-propionic acid as a white crystalline solid (7.82 g, 53%). 1H-NMR; δ (CDCl3), 7.61-7.15 (10 H, m), 4.66 (2 H, d, J=1.7 Hz), 3.13-2.94 (4 H, m), 2.84-2.74 (1 H, m). | |
25.1% | In ethanol; at 20℃; for 168h;Reflux; | A solution of Part D(1) compound (8.9 g, 54.9 mmoles) and O-benzylhydroxylamine (26.7 g, 0.23 mole) in absolute EtOH (9.0 ml) was refluxed for 7 days, cooled to room temperature and evaporated to dryness. The residual syrup was dissolved in 1.0 N NaOH (55 ml), stirred for 15 minutes then extracted with EtOAc (4×18 ml). The organic phase was washed with H2O (3×10 ml) and the aqueous extracts were combined and acidified to pH 2.0 with 1.0 N HCl (62 ml). The acidic aqueous phase was then extracted with EtOAc (5×75 ml) and the combined organic extracts washed with H2O (2×30 ml), dried (anhydrous Na2SO4), filtered, evaporated to dryness and dried in vacuo. The crude product (3.93 g, 25.1%) was triturated with Et2O:Hexane (1:4; 2×25 ml) and all solids obtained were dissolved in CH2Cl2 and filtered, washing the insoluble precipitates with CH2Cl2. The clear filtrate was evaporated and dried in vacuo to give title compound as an opaque colorless solid with consistent 1H-NMR and 13C-NMR spectral data. [00106] TLC: Rf 0.33 (Silica gel; CH2Cl2:MeOH-9:1; UV, PMA). [00107] M.p. 69-71 C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
at 20 - 50℃; for 2.5h; | 2-Benzylacrylic acid (2.55 g, 15.8 mmol) was dissolved in thioacetic acid (2.81 mL, 39.4 mmol). The solution was stirred for 90 min at rt, for 1 h at 50 C. and then concentrated. The crude product was purified by column chromatography (silica gel, hexanes/ethyl acetate). | |
23.8 g | at 30 - 60℃; | 16.2 g of 2-benzylacrylic acid and 12.3 ml of thioacetic acid were were charged into a clean and dry R.B.flask and stirred at about 30C for about 1 hour. The reaction mixture was heated to about 60C and stirred for about 4 hours.The excess of thioacetic acid was distilled off completely to afford the title compound as residue. Yield: 23.8 g |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92.8% | With ethanol; sodium hydroxide; In dichloromethane; at 10 - 20℃; for 3.5h;Reflux; | Then 500 ml of dichloromethane was added,20% sodium hydroxide solution 85 g and 50 g absolute ethanol,Temperature control 10-20 reaction 3.5 hours;After standing,Separate water,To the organic layer was added 45 g of concentrated hydrochloric acid to adjust pH = 1;Once again separate the water layer,The organic layer was washed with 300 ml of purified water,25 g of anhydrous sodium sulfate was added to the organic layer and dried to dryness under reduced pressure.Then add 150 g of absolute ethanol,Heating up,To the total dissolved after stirring down to -5 crystallization,filter,The filter cake was dried under reduced pressure at 40-50 C to give 59.1 g of a white crystalline solid,Purity 99.8%Yield 92.8%. |
80% | With water; sodium hydroxide; for 2h;Reflux; | In a 500 mL three-necked flask, 3-phenyl-1-benyne (11.6 g, 0.1 mol) was added.Ethyl carbonate (9g, 0.1moL),Pd2(dba)3 (0.46g, 0.01moL),Dppp (0.4g, 0.02moL),Finally, 200 mL of solvent anhydrous toluene was added, and the mixture was stirred under nitrogen for 10 min, and slowly heated to 100 C.Reaction for 24 hours.After the reaction was completed, the reaction solution was cooled to room temperature.The catalyst was filtered, then 100 mL of 20% NaOH solution was added, heated to reflux for 2 h, and cooled to room temperature to stand for stratification.Add concentrated hydrochloric acid to adjust pH=1, extract the aqueous phase with ethyl acetate, combine the organic phases, spin dry the solvent, and dry in vacuo;Recrystallization from ethanol gave 13 g of a white solid benzyl acrylate.The yield was 80%. MS (EI): m/z: 162.07 ([M]+). |
With sodium hydroxide; In ethanol; | (b) α-Benzylacrylic acid A mixture of α-benzylacrylic acid, ethyl ester (13.5 g., 0.071 mole), ethanol (140 ml.), and 1N sodium hydroxide (140 ml., 2 eq.) was stirred under argon at room temperature for 12 hours. The ethanol and some water was stripped and the residue washed with ethyl acetate and then acidified with concentrated hydrochloric acid to pH 1.0. The resulting oil was extracted into ethyl acetate, then washed with brine, dired (MgSO4), and evaporated to give 9.9 g. of α-benzylacrylic acid as a white crystalline solid; m.p. 61-62. Tlc (ethyl acetate:hexane; 3:1) major spot at Rf =0.8. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen bromide; acetic acid; In water; at 80℃; for 72h; | 2-Benzyl-2-hydroxymethyl-diethyl-malonate (11.2 g, 40.0 mmol) was dissolved in a mixture of 48% HBr (23 mL, 420 mmol) and acetic acid (7.6 mL, 130 mmol) and warmed to 80 C. After 3 days the solution was cooled to rt and diluted with dichloromethane. The organic layer was washed with water and brine, dried over MgSO4, filtered and evaporated. The crude product was purified by column chromatography (silica gel, hexanes/ethyl acetate). MS-(M-H-) 161.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | A solution of benzylmalonic acid (20.0 g, 0.103 mol, 1 eq) and paraformaldehyde (4.94 g, 0.164 mol, 1.6 eq) in ethyl acetate (150 mL) was cooled (0 C.) and treated with diethylamine (10.65 mL, 0.103 mol, 1 eq) drop wise, keeping the reaction temperature below 20 C. The reaction was then warmed to reflux for 90 minutes and cooled again on ice. The homogeneous solution was treated with water (20 mL) and concentrated aqueous HCl (12N) (9.0 mL, 0.108 mol) drop wise, keeping the reaction temperature below 10 C. The phases were then separated. The organic layer was washed with brine (100 mL), dried over sodium sulfate, filtered, and the filtrate concentrated under vacuum giving 2-methylene-3-phenylpropanoic acid (10) as a white solid (15 g, 90%). A solution of 10 (10.3 g, 63.5 mmol) in methanol (100 mL) was cooled on ice and treated dropwise with thionyl chloride (14.0 mL, 192 mmol). After warming to ambient temperature, the reaction was stirred for 18 hours at room temperature and concentrated in vacuo. The crude product was dissolved in diethyl ether, washed with a saturated aqueous solution of sodium bicarbonate and brine, dried over sodium sulfate, filtered, and the filtrate concentrated in vacuo providing the methyl ester 11 (11.2 g, 100%) as a pale yellow oil. To a solution of (+/-)2 (2 g, 8.643 mmol, 1 eq), 2-benzyl-acrylic methyl ester 11 (3.19 g, 0.0182 mol, 2.1 eq) in methanol (25 mL) was added triethylamine (3.54 mL, 25.93 mmol, 3 eq) and the solution was heated to reflux for 16 hours under argon. The reaction mixture was concentrated in vacuo, then dissolved in ethyl acetate (200 mL). The mixture was extracted with a 1N aqueous solution of hydrochloric acid (2×200 mL). The combined aqueous phase was alkalinized to pH 8 with solid sodium hydrogenocarbonate, then extracted with ethyl acetate (3×150 mL). The combined organic extracts were dried (sodium sulfate), filtered and concentrated in vacuo to afford a clear tan oil. This oil was purified by column chromatography (eluent:dichloromethane/methanol=98:2) affording the desired compound 12 (mixture of diastereoisomers) (1.07 g, 30.5%). To a stirred solution of 12 (0.265 g, 0.650 mmol, 1 eq) in anhydrous dichloromethane (3 mL) was added triethylamine (154 μL, 11.05 mmol, 1.7 eq), followed by drop wise addition of a solution of N-phenyltrifluoromethanesulfonimide (0.347 g, 0.975 mmol, 1.5 eq) in anhydrous dichloromethane (0.5 mL) at room temperature under argon. The reaction mixture was allowed to stir for 1 h at room temperature. Dichloromethane (20 mL) was added to the mixture, which was washed with a IN aqueous solution of sodium hydroxide (20 mL) and brine (20 mL). The organic layer was then dried (sodium sulfate), filtered, and concentrated in vacuo. The crude product was purified by column chromatography (eluent:dichloromethane) affording the desired compound 13 (mixture of diastereoisomers) (0.281 g, 80%). A mixture of triflate 13 (0.500 g, 0.927 mmol, 1 eq), diphenylphosphinoferrocene (DPPF) (77 mg, 15 mol %, 0.139 mmol), Pd2(dba)3 (42.5 mg, 5 mol %), sodium tert-butoxide (0.196 g, 2.04 mmol, 2.2 eq) and benzophenone imine (187 μL, 1.112 mmol, 1.2 eq) in anhydrous toluene (40 mL) was degassed using vacuum and argon. The mixture was then heated to 80 C. for 16 hours. The reaction mixture was cooled to room temperature and quenched by addition of an aqueous saturated solution of ammonium chloride (100 mL). The organic layer was separated. The aqueous layer was further extracted with dichloromethane (2×100 mL) and the combined organic extracts were washed with brine (100 mL) prior to drying with sodium sulfate, filtering, and concentration in vacuo. The crude imine 14 was used for the next step without further purification (0.460 g, 85%). A mixture of the crude imine 14 (0.4 g, 0.682 mmol, 1 eq), hydroxylamine hydrochloride (96.5 mg, 1.365 mmol, 2 eq), sodium acetate (282 mg, 3.425 mmol, 5 eq) in methanol (10 mL) was stirred at room temperature for 45 minutes. The reaction mixture was concentrated in vacuo and partitioned between dichloromethane (3×50 mL) and water (50 mL). The combined organic extracts were washed with brine (50 mL) and dried over sodium sulfate. The organic extracts were filtered and concentrated in vacuo. The crude product was purified by column chromatography (eluent:dichloromethane/methanol=99:1) affording the desired compound 15 (mixture of diastereoisomers) (0.295g, 100%). To a cooled (0 C.), stirred solution of the aniline derivative 15 (0.200 g, 0.492 mmol, 1 eq) and triethylamine (135μL, 0.983 mmol, 2eq) in anhydrous dichloromethane (10 mL) was added drop wise acetyl chloride (55 μL, 0.738 mmol, 1.5 eq). The mixture was stirred for 1 hour at room temperature and washed with an aqueous saturated solution of sodium hydrogenocarbonate. The aqueous layer was further extracted with dichloromethane (2×25 mL). The combined organic extracts were washed with brine (50 mL), then dried (sodium sulfate) prior to filtration and concentr... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In tiolacetic acid; benzene; | STEP A α-acetylthiomethyl-benzene-propanoyl chloride A solution of 1.21 g of α-benzyl-acrylic acid [described by Mannich et al, Chem. Ber., Vol. 57B (1924), p. 1116-8] in 0.8 g of thioacetic acid was held under argon at room temperature for one hour and was heated at 100 C. for one hour. Excess thioacetic acid was distilled under reduced pressure and 1.8 g of thionyl chloride was added dropwise with stirring under argon at 0 C. to the oil residue. The mixture was held overnight at room temperature and excess thionyl chloride was evaporated under reduced pressure. 50 ml of benzene were added to the residue and was evaporated under reduced pressure. The oil residue was distilled to obtain 1.87 g of α-acetylthiomethyl-benzene-propanoyl chloride with a boiling point of 150 C. at 10-2 Torr. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
A mixture of 28 mmol of the appropriate compound of formula VII and 2.9 ml of diethylamine was treated with 11 ml of formalin and heated to reflux temperature for 1-3 h. The solution was cooled to 20 C. diluted with CH2Cl2 and washed with aqueous NaHCO3. The aqueous layer was acidified to pH=1 using diluted hydrochloric acid and extracted with CH2Cl2. The combined organic layers were dried and evaporated to give the corresponding crude acrylic acid in 70 to 80% yield. To a solution of 4.3 mmol of the acrylic acid in 7 ml of tetrahydrofurane 560 mg of p-toluidine, 1.8 ml of NEt3, 950 mg of 1-hydroxybenzotriazole and 1.28 g of N-(3-dimethylaminopropyl)-N'-ethyl-carbodiimide hydrochloride were subsequently added and the suspension was stirred at 20 C. for 1-3 h. The mixture was partitioned between aqueous sat. NH4Cl and AcOEt, the organic layer was washed with 0.5 N aqueous NaOH, dried and evaporated. The crude material was chromatographed on silica using n-heptane/AcOEt to give the desired compound of formula VI in 50 to 70% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; ethyl acetate; N,N-dimethyl-formamide; | N-Benzyloxy-2-benzylacrylamide One drop of DMF was added to a mixture of 2-benzylacrylic acid (0.4g) (CAS No 5669-19-2) and oxalyl chloride (0.22 ml) in methylene chloride (5 ml) and the mixture was stirred for 30 minutes. The solvent was removed and methylene chloride (5 ml) was added and this, in turn, was removed. The residue was dissolved in methylene chloride (2 ml) and this was added to a solution of O-benzylhydroxylamine hydrochloride (0.39 g) and triethylamine (0.69 ml) in methylene chloride. The mixture was stirred for 1 hour, washed with water (2*10 ml) and dried. The residue obtained on removal of the solvent was passed down a Bond-elute column eluding with methylene chloride initially but then in a gradient with ethyl acetate (up to 10% ethyl acetate/methylene chloride) to give the title compound, yield 420 mg as a gum, M+H=268. 1H-NMR (CDCl3): 3.6 (s, 2H), 4.83 (s, 2H), 5.25 (s, 1H), 5.58 (s, 1H), 7.1-7.37 (m, 10H), 8.1 (s, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium hydroxide; formaldehyd; In methanol; ethanol; water; | (a) 2-Benzyl-acrylic Acid Diethyl benzylmalonate (100 g, 400 mmol) was dissolved in ethanol (300 mL) and treated with a solution of potassium hydroxide (134.4 g, 2.4 mol) in water (500 mL). The mixture was heated under reflux for 5 hours and then allowed to cool. Ethanol was removed under reduced pressure and the remaining aqueous solution cooled in ice and acidified to pH1 with concentrated HCl. The product was extracted with ethyl acetate (3*200 mL). The combined extracts were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to yield benzylmalonic acid as a white crystalline solid. The solid was taken-up in ethanol (250 mL) and treated portionwise with piperidine (33 g, 397 mmol) followed by an aqueous solution of formaldehyde (37%, 150 mL) which resulted in formation of a white precipitate. The reaction mixture was heated and treated with methanol (50 mL) to give a homogeneous solution. Following dissolution the reaction mixture was heated under reflux for 4 hours. The reaction mixture was concentrated under reduced pressure. The aqueous residue was acidified to pH1 with 1 M HCl and the product extracted with ethyl acetate (3*150 mL). The combined extracts were washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to yield 2-benzyl-acrylic acid as a colourless oil which crystallized on standing (45 g, 75%). 1H-NMR; δ (CDCl3), 7.32-7.17 (5H, m), 6.36 (1H, s), 5.54 (1H, d, J=1.3 Hz), 3.61 (2H, s). | |
With potassium hydroxide; formaldehyd; In methanol; ethanol; water; | Step A 2-Benzyl-acrylic Acid Diethyl benzylmalonate (100 g, 400 mmol) was dissolved in ethanol (300 mL) and treated with a solution of potassium hydroxide (134.4 g, 2.4 mol) in water (500 mL). The mixture was heated under reflux for 5 hours and then allowed to cool. Ethanol was removed under reduced pressure and the remaining aqueous solution cooled in ice and acidified to pH 1 with concentrated HCl. The product was extracted with ethyl acetate (3*200 mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield benzylmalonic acid as a white crystalline solid. The solid was taken-up in ethanol (250 mL) and treated portionwise with piperidine (33 g, 397 mmol) followed by an aqueous solution of formaldehyde (37%, 150 mL) which resulted in formation of a white precipitate. The reaction mixture was heated and treated with methanol (50 mL) to give a homogeneous solution. Following dissolution the reaction mixture was heated under reflux for 4 hours. The reaction mixture was concentrated under reduced pressure. The aqueous residue was acidified to pH 1 with 1 M HCl and the product extracted with ethyl acetate (3*150 mL). The combined extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to yield 2-benzyl-acrylic acid as a colorless oil which crystallized on standing (45 g, 75%). 1H-NMR; δ (CDCl3), 7.32-7.17 (5 H, m), 6.36 (1 H, s), 5.54 (1 H, d, J=1.3 Hz), 3.61 (2 H, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With potassium hydroxide; In methanol; | Step 9: Preparation of α-methylenebenzenepropanoic acid The ethyl α-methylenebenzenepropanoate of Step 8 (4.6 g, 24.3 mmol) was dissolved in methanol (12 mL) and then reacted with 2N potassium hydroxide (24 mL) solution. The mixture was stirred at room temperature for 4 hours and concentrated by evaporation. The residue was diluted with water and washed with ether. The aqueous layer was acidified to pH 2 with 1N HCl, and then extracted with ethyl acetate. The extracts were dried (MgSO4) and evaporated to give the title compound as colorless oil (2.8 g, 66% yield). 1 H NMR: 300MHz spectrum consistent with proposed structure. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.6% | In pyridine; thionyl chloride; toluene; | EXAMPLE 6 Preparation of N-(4-ethoxycarbonylmethyl-2-thiazolyl)-2-benzolyl)-2-propenamide <strong>[5669-19-2]2-Benzyl-2-propenoic acid</strong> (13 g; 0.080 moles) was dissolved in thionyl chloride (13 ml). After 24 hours at 20 C., the reaction mixture was evaporated to dryness and the residue was collected twice with toluene (50 ml), evaporating to dryness each time. An oil was obtained which was collected with pyridine (20 ml) and a solution of ethyl (2-amino-4-thiazolyl)acetate (14.92 g; 0.080 moles) in pyridine (160 ml) was added dropwise under nitrogen atmosphere. After one hour at room temperature the solvent was evaporated under vacuum and by chromatography on silica gel column (eluent hexane:ethyl acetate=6.4) N-(4-ethoxycarbonylmethyl-2-thiazolyl)-2-benzyl-2-propenamide (20 g; 75.6% yield) was obtained as oil. 1 H-NMR (200 MHz, CDCl3): δ (ppm): 1.24 (t, 3H); 3.65 (s, 2H); 3.74 (s, 2H); 4.16 (q, 2H); 5.46 (m, 1H); 5.94 (s, 1H); 6.78 (s, 1H); 7.25 (m, 5H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | In CaCl2; | Stage 1: 2-Acetylthiamethyl-3-phenylpropanoic acid 10 g of benzylacrylic acid Ia (61.7 mmol) and 7.1 ml of thioacetic acid (1.6 eq.) are placed in a round bottom flask fitted with a condenser and a CaCl2 trap. The mixture is heated to 70 C. with stirring for 24 h. The excess thioacetic acid is evaporated off under vacuum (1 mm, 60 C.). The yellow pasty residue is taken up three times with 50 ml of ether. Each time the ether is evaporated off at normal pressure and then the residue is dried under vacuum. These stages are intended to remove the remaining traces of thioacetic acid. 14 g of a very viscous yellow oil are obtained (Yield=95 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With bis-(trimethylsilyl)acetamide; In dichloromethane; ethyl acetate; | A. α-[(Diethoxyphosphinyl)methyl]benzenepropanoic acid Bis(trimethylsilyl)acetamide (5 g, 0.024 mole, 6 ml) was added, at room temperature, to a solution of benzyl acrylic acid (2 g, 0.012 mole) and diethyl phosphite (3.3 g, 0.024 moles) in dichloromethane (30 ml). The mixture was stirred at ambient temperature for 30 minutes, concentrated in vacuo at room temperature, and the residue was heated at a bath temperature of 100-110 for 16 hours. The colorless oil reaction mixture was dissolved in ethyl acetate and extracted with 5% sodium bicarbonate (pH 9-10). The aqueous alkaline solution was washed with ether and acidified to a pH of 1-2 with concentrated hydrochloric acid. The colorless oil that separated was extracted into ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give a colorless oil (3.6 g). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.03 g (95%) | In methanol; | Methyl alpha-Benzylacrylate. alpha-Benzylacrylic acid (1.00 g, 6.17 mmol) in methanol (20 ml) was treated with BF3.Et2 O (2 ml). The mixture was heated to reflux for 14 h, cooled, and poured into saturated NaHCO3 solution. Extraction with ether followed by drying over Na2 SO4 and evaporation afforded 1.03 g (95%) of a mobile oil. 1 H NMR (CDCl3) delta7.17-7.35 (m,5H), 6.23 (m,1H), 5.47 (m,1H), 3.74 (s,3H), 3.63 (s,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.03 g (95%) | In methanol; | A. Methyl a-Benzylacrylate a-Benzylacrylic acid (1.00 g, 6.17 mmol) in methanol (20 ml) was treated with BF3 *Et2 O (2 ml). The mixture was heated to reflux for 14 h, cooled, and poured into saturated NaHCO3 solution. Extraction with ether followed by drying over Na2 SO4 and evaporation afforded 1.03 g (95%) of a mobile oil. 1 H NMR (CDCl3) delta 7.17-7.35 (m,5H), 6.23 (m,1H), 5.47 (m,1H), 3.74 (s,3H), 3.63 (s,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
(C) 3-(Acetylthio)-2-(phenylmethyl)propionic acid Following the procedure of Example 1B, but substituting benzylacrylic acid for 4-methyl-2-methylenepentanoic acid, yields the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; | EXAMPLE 32 3-Acetylthio-2-benzylpropanoic acid chloride 2-Benzylacrylic acid (8.1 g.) and thiolacetic acid (5.3 g.) are mixed and heated on the steam bath for one hour. After cooling to room temperature, thionyl chloride (9.75 g.) is added and the mixture is stored overnight at room temperature. The excess thionyl chloride is removed in vacuo and the residue is distilled to obtain 3-acetylthio-2-benzylpropanoic acid chloride b0.05:120-122. | |
With thionyl chloride; | EXAMPLE 32 3-Acetylthio-2-benzylpropanoic acid chloride 2-Benzylacrylic acid (8.1 g.) and thiolacetic acid (5.3 g.) are mixed and heated on a steam bath for 1 hour. After cooling to room temperature, thionyl chloride (9.75 g.) is added and the mixture is stored overnight at room temperature. The excess thionyl chloride is removed in vacuo and the residue is distilled to obtain 3-acetylthio-2-benzylpropanoic acid chloride b0.05:120-122. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With thionyl chloride; In water; | (a) 2-Phenylmethyl-2-propenoyl chloride Benzyl malonic acid (13 g., 0.067 mole) is mixed with 40% aqueous dimethylamine (7.6 g., 0.068 mole) and 37% formalin (5.4 g., 0.068 mole) in 150 ml. of water. The voluminous solid which forms in 15 minutes is filtered after two hours, washed with water and dried partially in air to give 20.8 g. of benzyl malonic acid dimethylamine. This solid is melted in a 170 oil bath and heated for 10 minutes until amine evolution stops and bubbling virtually ceases. The cooled product, a mobile liquid, is acidified with 10% potassium bisulfate, extracted with hexane, dried (Na2 SO4) and evaporated to give 6.3 g. of solid 2-benzylacrylic acid. The 2-benzylacrylic acid (6.0 g.) is dissolved in ether and 10 ml. of thionyl chloride are added dropwise. Reaction temperature is allowed to rise to 35. After stirring for 2 hours, the mixture is concentrated in vacuo to yield 6.4 g. of crude 2-phenylmethyl-2-propenoyl chloride. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; | Example II preparation of enantiomerically enriched (S)-3-thioacetyl-2-benzyl propionic acid To 90 ml of toluene, 110 mg (1 mmol) of <strong>[5536-61-8]sodium methacrylate</strong> and 3.24 g (20 mmol) of 2-benzylacrylic acid were added at 70ØC. The resulting mixture was stirred for 15 minutes, followed by the addition of 8.5 ml of the catalyst solution prepared in example 1 (2.8 mmol Ti-catalyst) at 70ØC. The mixture was stirred for an additional 15 minutes at 70ØC. 1.56 ml (22.7 mmol) of thioacetic acid was dosed to the reaction mixture at 70ØC within 15 minutes. The reaction mixture was stirred for 1 hour at 70ØC to complete the conversion. Thee.e. of (S)-3-thioacetyl-2-benzylpropionic acid in the reaction mixture, as determined by HPLC, was 44%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.03 g (95%) | In methanol; | Example 160 Methyl alpha-Benzylacrylate. alpha-Benzylacrylic acid (1.00 g, 6.17 mmol) in methanol (20 ml) was treated with BF3·Et2O (2 ml). The mixture was heated to reflux for 14 h, cooled, and poured into saturated NaHCO3 solution. Extraction with ether followed by drying over Na2SO4 and evaporation afforded 1.03 g (95%) of a mobile oil. 1H NMR (CDCl3)delta 7.17-7.35 (m,5H), 6.23 (m,1H), 5.47 (m,1H), 3.74 (s,3H), 3.63 (s,2H). |
1.03 g (95%) | In methanol; | Example 110 Methyl alpha-Benzylacrylate. alpha-Benzylacrylic acid (1.00 g, 6.17 mmol) in methanol (20 ml) was treated with BF3·Et2O (2 ml). The mixture was heated to reflux for 14 h, cooled, and poured into saturated NaHCO3 solution. Extraction with ether followed by drying over Na2SO4 and evaporation afforded 1.03 g (95%) of a mobile oil. 1H NMR (CDCl3) delta 7.17-7.35 (m,5H), 6.23 (m,1H), 5.47 (m,1H), 3.74 (s,3H), 3.63 (s,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.6% | In pyridine; thionyl chloride; toluene; | Example 6 Preparation of N-(4-ethoxycarbonylmethyl-2-thiazolyl)-2-benzyl-2-propenamide <strong>[5669-19-2]2-Benzyl-2-propenoic acid</strong> (13 g; 0.080 moles) was dissolved in thionyl chloride (13 ml). After 24 hours at 20C, the reaction mixture was evaporated to dryness and the residue was collected twice with toluene (50 ml), evaporating to dryness each time. An oil was obtained which was collected with pyridine (20 ml) and a solution of ethyl (2-amino-4-thiazolyl)acetate (14.92 g; 0.080 moles) in pyridine (160 ml) was added dropwise under nitrogen atmosphere. After one hour at room temperature the solvent was evaporated under vacuum and by chromatography on silica gel column (eluent hexane: ethyl acetate=6:4) N-(4-ethoxycarbonylmethyl-2-thiazolyl)-2-benzyl-2-propenamide (20 g; 75.6% yield) was obtained as oil. 1H-NMR (200 MHz, CDCl3): δ (ppm): 1.24 (t, 3H); 3.65 (s, 2H); 3.74 (s, 2H); 4.16 (q, 2H); 5.46 (m, 1H); 5.94 (s, 1H); 6.78 (s, 1H); 7.25 (m, 5H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride; In ethanol; | (c) [(2-Carboxy-3-phenylpropyl)ethoxyphosphinyl]acetic acid, methyl ester A mixture of α-benzylacrylic acid (5.0 g., 30.8 mmole) and carbomethoxymethyldichlorophosphine (4.5 ml., 1.6 eq.) under argon was heated at 65 for 18 hours. The flask was then equipped with a short path still, acetic anhydride (6.4 ml., 2.0 eq.) was added, and the temperature was increased to 85. After 2.5 hours, acetyl chloride was no longer distilling and the excess acetic anhydride and acetyl chloride were removed in vacuo. Ethanol (6 ml.) was added to the residue and the resulting mixture was stirred at 60 for 2 hours. The ethanol was then stripped to leave a residue (12.4 g.) which was chromatographed on silica (300 g.) eluding with (dichloromethane/acetic acid/methanol; 100/2.5/2.5) to give 2.2 g. of [(2-carboxy-3-phenylpropyl)ethoxyphosphinyl]acetic acid, methyl ester as a colorless oil. Tlc (dichloromethane/acetic acid/methanol; 100/5/5) single spot at Rf =0.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
The chiral catalyst [Show Image] is used, the asymmetric catalytic hydrogenation of 2- benzyl acrylic acid 7 is carried out under the condition same to that of Embodiment 5, the result of the reaction is that: the conversion rate is 100%, the yield is 93% and the ee value of the product is 73%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With C54H72IrNP(1+)*C32H12BF24(1-); hydrogen; caesium carbonate; In methanol; at 45℃; under 4500.45 Torr; for 0.25h;Glovebox; | General procedure: Example 12 Hydrogenation of Alpha-Substituted Acrylic Acid at the Hydrogen Pressure of 0.6 MPa The catalyst (S)-5a (0.9 mg, 0.0005 mmol), alpha-substituted acrylic acid 6 (0.5 mmol) and cesium carbonate (82 mg, 0.25 mmol) were weighed from glove box and transferred into the reaction inner tube containing a stir bar. The tube was sealed as a spare. Methanol (2 mL) was injected into the tube with syringe after fetching out the tube. The inner tube was placed in the hydrogenation reaction still. The original atmosphere was displaced with hydrogen atmosphere by inflating-deflating operation (3-5 times). The hydrogen pressure was ultimately set at 0.6 MPa. At the temperature of 45, the reaction was proceeded with stirring until the pressure stopped decreasing. After stopping stirring to release hydrogen and concentrating the system with rotary steaming, the pH value of the system was adjusted with 3 N hydrochloric acid until pH<3. The mixture was extracted by ether (10 mL 3). The organic phases merged together were washed by sodium chloride solution and dried by anhydrous sodium sulfate. The drying agent was removed by suction filtration. The target product (R) 7 was obtained after solvent was removed by rotary steaming. The conversion rate was analyzed by 1H NMR proving that all of the reactions were converted completely. The ee value was analyzed by chiral GC, chiral HPLC or chiral SFC after the product was transformed into corresponding methyl ester. The experimental results determined are listed in Table 6. |
94% | In the glove box, the catalyst [(Sa-DTB-SIPHOX)Ir(COD)]BARF 4 (2.4 mg, 0.00125 mmol) , 2- benzyl acrylic acid 7 (81 mg, 0.5 mmol) and cesium carbonate (82 mg, 0.25 mmol) are weighted in the reaction inner tube with stirring bar, then the reaction inner tube is sealed for use. When the reaction inner tube is took out, anhydrous methanol (2 mL) is added with a syringe, then the inner tube is placed into the hydrogenation reactor, the mixture is stirred at room temperature under the hydrogen pressure of 0.6 Mpa to react for 12 h. Then the stirring is stopped, the hydrogen is released. After the system is condensed by evaporating off rotatably, the system is adjusted pH <3 with 3N hydrochloric acid water solution, extracted with diethyl ether (10 mL × 3), and separated, the organic phase is collected, washed with saturated salt water, and dried with anhydrous sodium sulfate. The desiccant is removed by suction filtration, the solvent is evaporated off by rotating, then the object product 8 is obtained, and is a colorless oily liquid, through the 1H NMR analysis, the conversion rate is 100% and the yield is 94%.[α]30,D -31.9 (c 1.0, CH2Cl2); 1H NMR (400 MHz, CDCl3): δ 9.95 (brs, 1H, COOH), 7.31-7.18 (m, 5H, Ar-H), 3.08 (dd, J = 13.2 and 6.4 Hz, 1H, CH2), 2.77 (sextet, J = 6.8 Hz, 1H, CH), 2.67 (dd, J = 13.2 and 8.0 Hz, 1H, CH2), 1.18 (d, J = 6.8 Hz, 3H, CH3); after it is converted to phenyl amide, its ee value is 91 % through the chiral SFC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Example -1 : Preparation of 2-(benzyl acrylolyl amino) acetic acid benzyl ester (la) using ethyl chloro formate50gms of 2-benzyl acrylic acid, 500ml. of dichloromethane and 34.3 gms of triethylamine were charged in a clean and dry 1 lit. 4 neck R.B. flask. The reaction mass was cooled to about -5 C and 36.84 gms of ethylchloroformate was added drop-wise at about -5 C and stirred for about 30min. at the same temperature . After completion of the reaction, 104.03gr. of glycine benzyl ester p-tosylate, 34.3gr. of triethylamine and 200ml. of dichloromethane were added at -5 C and stirred for 1 hr 30min. at the same temperature. After completion of reaction, the reaction mass was brought to about 25 C and stirred for 30min. he reaction mass was washed with 250ml. of water followed by 250ml. of 4% sodium bicarbonate solution and again with 250ml. of water. The organic layer was separated and washed with 4 gms of carbon. The resulted reaction solution was distilled ordinarily and then finally under vacuum. Then charged 75ml. of isopropyl alcohol and distilled under vacuum upto 80C to obtain 2-(benzylacryloyl amino)acetic acid benzyl ester as the residue.Wt: 104gr.To the 104gr. of residue, added 104ml. of isopropyl alcohol and 104ml. of n-hexane at ambient temperature. The resulted solution was cooled to 0-5C and stirred for 30min. at the same temperature. The resulted solution was filtered and washed with 50ml. of n-hexane to obtain the 2-(benzylacryloyl amino)acetic acid benzyl ester as a pure solid.Yield: 50-53gr. Purity by HPLC: 99.8%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In toluene; at 80℃; for 9h; | A solution of 10 (1.00 g, 4.52 mmol), 2-methylene-3-phenylpropionic acid (19, 1.47 g, 9.04 mmol), DMAP (55.0 mg, 0.45 mmol), and EDCI (2.60 g, 13.5 mmol) in dry PhMe (45 mL) was heated at 80C with stirring for 9 h and quenched with water. The reaction was quenched by water and the reaction mixture was extracted with EtOAc (50mL×3). The combined organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography (silica gel, 16.7% EtOAc in hexane) to give 13c (1.57g, 95%) as a colorless oil. Rf=0.40 (25% EtOAc in hexane); IR (film): 2969, 1737, 1635, 1439, 1341, 1206, 1100cm-1; 1H NMR (400MHz, CDCl3) δ 7.36-7.20 (m, 8H), 7.14 (d, J=8.0Hz, 1H), 6.49 (s, 1H), 5.64 (d, J=0.8Hz, 1H), 3.76-3.66 (m, 3H), 3.44 (septet, J=6.8Hz, 1H), 1.53 (d, J=6.8Hz, 3H), 1.44 (d, J=6.8Hz, 3H), 1.06 (d, J=6.8Hz, 3H), 0.95 (d, J=6.4Hz, 3H); 13C NMR (100MHz, CDCl3) δ 166.9, 165.0, 146.7, 139.5, 138.3, 131.7, 129.4, 129.3 (×2), 128.6 (×2), 128.5, 126.5, 126.4, 125.9, 123.2, 50.9, 45.9, 38.1, 20.9, 20.5, 20.4, 20.34; HRMS (+CI) calcd for C23H28NO3 366.2069 (M+H+), found 366.2073. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With tris(triphenylphosphine)ruthenium(II) chloride; C52H46F12N2O2P2Ru; hydrogen; potassium hydroxide; In methanol; at 0℃; under 22502.3 Torr; for 5h;Autoclave; | In a 10 ml of flask, added in advance phosphine nitrogen biligand L12c and triphenylphosphine ruthenium complex ( good catalyst) (3.4 mg, 2 . 0μmol), by adding α-substituted acrylic acid 1n (29.6 mg, 0 . 2mmol) with anhydrous potassium hydroxide(8.4 mg, 0 . 1mmol), and through the vacuum line system, nitrogen replacement was done for 3 times. The new injector and new degassed methanol (3 ml) containing substrate and the additive is injected into the reaction tube, the reaction system in the high-pressure autoclave, in 0 C and H 2 (30bar) stirring under the conditions of 5 hours, to remove the solvent under reduced pressure, heating a small amount of the mixed system nuclear magnetic resonance to determine the conversion rate. The rest of the arch column chromatography separation, to obtain pure product 2n. The conversion is 100%, the enantiomeric excess value 96% ee. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1.03 g (95%) | In methanol; | Example 208 Methyl alpha-Benzylacrylate. alpha-Benzylacrylic acid (1.00 g, 6.17 mmol) in methanol (20 ml) was treated with BF3·Et2O (2 ml). The mixture was heated to reflux for 14 h, cooled, and poured into saturated NaHCO3 solution. Extraction with ether followed by drying over Na2SO4 and evaporation afforded 1.03 g (95%) of a mobile oil. 1H NMR (CDCl3) delta 7.17-7.35 (m,5H), 6.23 (m,1H), 5.47 (m,1H), 3.74 (s,3H), 3.63 (s,2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | at 100℃; for 2h; | Add benzylacrylic acid (13 g, 0.08 moL) thioacetic acid (7.3 g, to a 500 mL three-neck reaction flask.0.096 moL), stirred at 100 C for 2 h;After the reaction is completed, the reaction solution is cooled to room temperature, a portion of the thioacetic acid is distilled off under pressure, and then thioacetic acid is completely removed by further pressurizing distillation by adding 100 mL of a toluene solvent.Recrystallization from ethanol gave 17 g of 2-acetylthiomethyl-3-phenylpropanoic acid as a white solid.The yield was 90%. MS (EI): m/z: 238.07 ([M]+). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane; at 100 - 110℃; for 2h; | Add 1.62g of 2-benzylacrylic acid to the reaction flask, add 1.38g of dithioacetic acid, then raise the temperature to 100-110 C, keep it for 2 hours, and distill dithioacetic acid under reduced pressure to obtain intermediate 2-benzyl-3-(ethylthiothio)propionic acid; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With (pentamethylcyclopentadienyl)*Rh(OAc)2; In 1,2-dichloro-ethane; at 60℃; for 9h; | The replacement reaction temperature was 60 C, and other experimental steps and purification methods were carried out according to Example 1; 9h, 62 mg of yellow solid 3ab was obtained, melting point 43-45 C, yield: 91%.Compound 1a (0.6mmol, 3.0eq),Cp * Rh (OAc) 2-H2O (0.02mmol, 0.1eq),Compound 2a (0.2mmol, 1.0eq),Reaction at 60 C until passing through the thin layer plate(TLC) Monitor the complete disappearance of raw material 2a (about 9h);Spin the solvent,Column chromatography separation (eluent:Petroleum ether / ethyl acetate volume ratio 2: 1),55 mg of yellow solid 3aa was obtained,Melting point 61-63 C, yield: 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With (pentamethylcyclopentadienyl)*Rh(OAc)2; In 1,2-dichloro-ethane; at 60℃; for 9h; | Substitute other experimental steps and purification methods according to the steps of Example 1; 9h, 70mg white solid was obtained, melting point 79-81 C, conversion rate: 87%.Compound 1a (0.6mmol, 3.0eq),Cp * Rh (OAc) 2-H2O (0.02mmol, 0.1eq),Compound 2a (0.2mmol, 1.0eq),Reaction at 60 C until passing through the thin layer plate(TLC) Monitor the complete disappearance of raw material 2a (about 9h);Spin the solvent,Column chromatography separation (eluent:Petroleum ether / ethyl acetate volume ratio 2: 1),55 mg of yellow solid 3aa was obtained,Melting point 61-63 C, yield: 85%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | With (pentamethylcyclopentadienyl)*Rh(OAc)2; In 1,2-dichloro-ethane; at 60℃; for 9h; | The substitution reaction temperature was 60 C. Other experimental steps and purification methods were carried out in accordance with the steps of Example 1; 9h, 63 mg of a yellow solid was obtained with a melting point of 47-49 C and a yield of 79%.Compound 1a (0.6mmol, 3.0eq),Cp * Rh (OAc) 2-H2O (0.02mmol, 0.1eq),Compound 2a (0.2mmol, 1.0eq),Reaction at 60 C until passing through the thin layer plate(TLC) Monitor the complete disappearance of raw material 2a (about 9h);Spin the solvent,Column chromatography separation (eluent:Petroleum ether / ethyl acetate volume ratio 2: 1),55 mg of yellow solid 3aa was obtained,Melting point 61-63 C, yield: 85%. |
Tags: 5669-19-2 synthesis path| 5669-19-2 SDS| 5669-19-2 COA| 5669-19-2 purity| 5669-19-2 application| 5669-19-2 NMR| 5669-19-2 COA| 5669-19-2 structure
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P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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