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CAS No. : | 31508-44-8 | MDL No. : | MFCD06795946 |
Formula : | C10H12O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | - |
M.W : | 164.20 | Pubchem ID : | - |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.3 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 47.11 |
TPSA : | 26.3 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) : | -5.5 cm/s |
Log Po/w (iLOGP) : | 2.23 |
Log Po/w (XLOGP3) : | 2.54 |
Log Po/w (WLOGP) : | 1.96 |
Log Po/w (MLOGP) : | 2.29 |
Log Po/w (SILICOS-IT) : | 2.21 |
Consensus Log Po/w : | 2.25 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.63 |
Solubility : | 0.385 mg/ml ; 0.00234 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.74 |
Solubility : | 0.299 mg/ml ; 0.00182 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.9 |
Solubility : | 0.207 mg/ml ; 0.00126 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.72 |
Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 | UN#: | |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
95% | With carbon tetrabromide at 20℃; for 25h; UV-irradiation; | |
95.49% | With thionyl chloride at 0 - 20℃; for 3h; | A Step A: methyl 2-phenylpropanoate To a solution of 2-phenylpropanoic acid (5 g, 33.33 mmol) in MeOH (15 mL) , sulfoxide chloride (5.15 g, 50 mmol) was added dropwise at 0 . After the addition, the reaction mixture was stirred at rt for 3h. The mixture was concentrated, quenched with ice water (20 mL) , extracted with EtOAc (30 mL x 3) . The combined organic layers were washed with brine, dried over Na 2SO 4, concentrated and purified by column chromatography (petroleum ether/EtOAc=20: 15: 1) to give methyl 2-phenylpropanoate (5.22 g, 95.49%) as yellow oil. MS: M/e 165 (M+1) +. |
95.49% | With thionyl chloride at 0 - 20℃; | A Step A: methyl 2-phenylpropanoate To a solution of 2-phenylpropanoic acid (5 g, 33.33 mmol) in MeOH (15 mL) , sulfoxide chloride (5.15 g, 50 mmol) was added dropwise at 0 . After the addition, the reaction mixture was stirred at rt for 3h. The mixture was concentrated, quenched with ice water (20 mL) , extracted with EtOAc (30 mL x 3) . The combined organic layers were washed with brine, dried over Na2SO4, concentrated and purified by column chromatography (petroleum ether/EtOAc =20: 1 5: 1) to give methyl 2-phenylpropanoate (5.22 g, 95.49%) as yellow oil. MS: M/e 165 (M+1) +. |
93% | With carbon tetrabromide for 13h; Heating; | |
90% | Stage #1: methanol With acetyl chloride at 0 - 20℃; for 0.166667h; Stage #2: hydratropic acid at 20℃; for 3.25h; Heating / reflux; | 9; 27 Methyl 2-phenylpropanoate Under nitrogen atmosphere, acetyl chloride was slowly added to 100 ml of methanol at 0° C. The solution was stirred for 10 min at 0° C., then warmed up to room temperature. The 2-phenylpropionic acid (146.07 mmol, 2 eq) was slowly added, the reaction mixture was stirred at room temperature for 15 min then heated to reflux for 3 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, buffer pH 7 then water. The organic layer was dried on sodium sulphate and evaporated to give intermediate 9 (11 g; 90%), which was a yellow oil. Intermediate 9 was characterized by the following spectroscopic data: 1H NMR (d6-DMSO, 400 MHz) δ (ppm) 1.52 (d, J=7.24 Hz, 3H), 3.67 (s, 3H), 3.74 (q, J=7.24 Hz, 1H), 7.26-7.34 (m, 5H).; Intermediate 272-phenylpropionic acid methyl ester Under nitrogen atmosphere, acetyl chloride was slowly added to 100 ml of methanol at 0° C. The solution was stirred for 10 min at 0° C., then warmed up to room temperature. The 2-phenylpropionic acid (146.07 mmol) was slowly added, the reaction mixture was stirred at room temperature for 15 min then heated to reflux for 3 hours. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, washed with water, buffer pH 7 then water. The organic layer was dried on sodium sulphate and evaporated to give intermediate 27, which was a yellow oil. Intermediate 27 was characterized by the following spectroscopic data: 1H NMR (DMSO-d6, 400 MHz) δ (ppm) 1.52 (d, J=7.24 Hz, 3H), 3.67 (s, 3H), 3.74 (q, J=7.24 Hz, 1H), 7.26-7.34 (m, 5H). |
88% | With sulfuric acid at 65℃; for 72h; | |
79% | With sulfuric acid Reflux; | |
76% | With boron trifluoride methanol complex for 8h; Heating; | |
60% | With nickel dichloride for 17h; Heating; | |
54% | With tert.-butylnitrite at 40℃; for 48h; Green chemistry; | |
28% | With 4-(dihydroxyboranyl)-1-methylpyridin-1-ium iodide for 20h; Heating; | |
With hydrogenchloride | ||
With thionyl chloride | ||
With sulfuric acid Heating; | ||
With sulfuric acid for 6h; Heating; | ||
With sulfuric acid for 5h; Heating; | ||
8.64 g | With toluene-4-sulfonic acid for 168h; Heating; | |
With sulfuric acid at 55℃; for 18h; | ||
at 63℃; for 4h; Inert atmosphere; | 2.a a) Methyl 2-phenylpropanoate; (+/-)-2-Phenylpropionic acid (20.5g) was dissolved in methanol (62mL) in a reaction vessel. Sulfuric acid (98%, 0.82mL) was then charged followed by methanol (20.5mL) as a line rinse. The reaction was then heated to 63°C (+/-3°C) and stirred at this temperature for up to 4hrs. The reaction was monitored by HPLC analyzing the methyl 2- phenylpropanoate: (+/-)-2-phenylpropionic acid ratio (specification >;97:3). Upon completion the reaction mixture was cooled to 23°C (+/-3°C). Cyclohexane (102mL) was added followed by Na2CO3 (aq) (3.7% wt/wt, 61.5mL). Layers were allowed to separate and the lower aqueous phase discarded. Water (61.5mL) was then charged and the mixture stirred for lOmins before the layers were separated discarding the lower aqueous phase. Cyclohexane (205mL) was then charged to the organic phase. The reaction mixture was then distilled under reduced pressure at 45°C, 150-240mbar removing 18OmL solvent. The reaction mixture was then cooled to 23°C (+/-3°C) yielding methyl 2-phenylpropanoate in a solution in cyclohexane. | |
With sulfuric acid Reflux; | ||
With thionyl chloride at 0 - 20℃; | ||
With bromobenzene; hydrogen at 40℃; for 3h; Autoclave; | 2.2 General procedure for catalytic esterification of carboxylic acid and transesterification reaction General procedure: In a typical run, a 50 mL stainless steel autoclave equipped with a transducer for online pressure monitoring was charged under air of Pd-pol (10.6 mg, Pd: 0.5 mol%), the substrate (carboxylic acid or ester, 1.0 mmol), bromobenzene (0.1 mmol, 15.7 mg) and alcohol (5.0 mL). The autoclave was then purged three times with hydrogen, then pressurized with 2 bars H2, set on a magnetic stirrer and heated to 40 °C. After the minimum time needed to reach reaction completion, the autoclave was let to reach room temperature, the hydrogen was vented and the autoclave opened. When necessary, 3.0 mL diethyl ether was added to the mixture at the end of reaction in order to dissolve organic reactants and products. The catalyst was recovered by centrifugation. The yields were assessed by GLC analysis of the organic solution by using biphenyl (50.0 mg) as internal standard. | |
With sulfuric acid at 65℃; | ||
With hydrogenchloride In water Reflux; | ||
With sulfuric acid at 65℃; | ||
With sulfuric acid | ||
With thionyl chloride at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With methanol; N,N,N,N,N,N-hexamethylphosphoric triamide; samarium diiodide In tetrahydrofuran at 20 - 22℃; for 12h; | |
With ethanol; nickel |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 2-phenylpropionic acid methyl ester With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran at 20℃; for 20h; | |
72% | Stage #1: 2-phenylpropionic acid methyl ester With lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at 20℃; for 20h; | |
72% | Stage #1: 2-phenylpropionic acid methyl ester With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 20℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at 20℃; for 20h; |
72% | Stage #1: 2-phenylpropionic acid methyl ester With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78 - 0℃; for 2h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at 20℃; for 20h; | |
With lithium diisopropyl amide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With 2-pyrrolidinon In N,N-dimethyl-formamide at 20℃; Flow reactor; | |
84% | With 1) EGB.2 at -78℃; other methyl arylacetates, other halogenides; | |
83% | With sodium hydride In tetrahydrofuran for 3h; Reflux; |
With ammonia; sodium amide | ||
With 1) EGB.2 1) -78 deg C, 2) -78 deg C, 15 min; Yield given. Multistep reaction; | ||
With sodium hexamethyldisilazane In tetrahydrofuran | ||
Stage #1: benzeneacetic acid methyl ester With potassium hexamethylsilazane In 1,2-dimethoxyethane; toluene at -78℃; Stage #2: methyl iodide In 1,2-dimethoxyethane; toluene at -78℃; Further stages.; | ||
With n-butyllithium; ammonium chloride; diisopropylamine In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane; water | R.77 Methyl 2-phenylpropionate (77) STR96 REFERENCE EXAMPLE 77 Methyl 2-phenylpropionate (77) STR96 A solution of n-butyl lithium in hexane (1.44N, 75 ml, 108 mmol) was added to a solution of diisopropylamine (11.3 g, 112 mmol) in anhydrous THF (200 ml) cooled at -20° C. under argon atmosphere, and the mixture was stirred for 30 minutes. The reaction mixture was cooled to -78° C. To this solution were added a solution of methyl phenylacetate (12.0 g, 80.0 mmol) in 15 ml of anhydrous THF and HMPA (20.6 g, 115 mmol). The mixture was stirred at -78° C. for 1 hour and then at -30° C. for 30 minutes. To this reaction solution was added a solution of methyl iodide (17.0 g, 120 mmol) in anhydrous THF (30 ml) at -78° C., and the mixture was stirred at -78° C. for 1.5 hours. The reaction mixture was allowed to warm to room temperature and diluted with an aqueous saturated solution of ammonium chloride (300 ml) and water (150 ml). The mixture was extracted with ether (400 ml). The aqueous layer was further extracted with ether (200 ml*2). The combined organic layers were washed with water (200 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 92°-93° C./10 mmHg) to give an oil of methyl 2-phenylpropionate (11.3 g, 68.9 mmol, 86.1%). This compound was assigned to the structure by the following data: IR(Liquid film method): 3080, 3040, 2990, 2960, 1730, 1600, 1490, 1450, 1430, 1370, 1330, 1250, 1210, 1160, 1100, 1070, 1030, 1010, 970, 910, 860, 810, 770, 730, 700 cm-1. NMR(90 MHz, CDCl3, δ): 1.50(3H, d, J=7.3 Hz), 3.65(3H, s), 3.72(1H, q, J=7.3 Hz), 7.1-7.4(5H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium; ammonium chloride; diisopropylamine; In tetrahydrofuran; N,N,N,N,N,N-hexamethylphosphoric triamide; hexane; water; | REFERENCE EXAMPLE 78 Methyl 2-methyl-2-phenylpropionate (78) STR97 A solution of n-butyl lithium in hexane (1.44N, 60.0 ml, 86.4 mmol) was added to a solution of diisopropylamine (9.07 g, 89.6 mmol) in anhydrous THF (200 ml) cooled at -30 C. under argon atmosphere, and the mixture was stirred for 20 minutes. To this reaction mixture were added a solution of methyl 2-phenylpropionate (10.5 g, 64.0 mmol) in 10 ml of anhydrous THF and HMPA (16.5 g, 92.0 mmol), and the mixture was stirred at -30 C. for 10 minutes and then at 0 C. for 45 minutes. To this reaction solution was added a solution of methyl iodide (13.6 g, 96.0 mmol) in anhydrous THF (30 ml) at -30 C., and the mixture was stirred at -30 C. for 1 hour. This reaction mixture was added to an aqueous saturated solution of ammonium chloride (400 ml) and water (50 ml) was added. The mixture was extracted with ether (400 ml). The aqueous layer further extracted with ethyl acetate. The combined organic layers were washed with water (300 ml) and brine, dried over anhydrous magnesium sulfate, and concentrated. The residue was distilled (b.p. 99-100 C./6 mmHg) to give an oil of methyl 2-methyl-2-phenylpropionate (7.63 g, 42.9 mmol, 67.0%). This compound was assigned the structure by the following data: IR(Liquid film method): 2970, 1730, 1600, 1500, 1450, 1390, 1370, 1250, 1190, 1150, 1100, 1080, 1030, 1020, 990, 850, 770, 740, 700 cm-1. NMR(90 MHz, CDCl3, delta): 1.58(6H, s), 3.64(3H, s), 7.1-7.4(5H, m). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With bis[1,2-bis(diphenylphosphino)ferrocene]-palladium(0); thallium(I) acetate In tetrahydrofuran Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With manganese; (2,2'-bipyridine)nickel(II) dibromide; trifluoroacetic acid In N,N-dimethyl-formamide at 20℃; for 1h; | |
69% | With (2,2'-bipyridine)nickel(II) dibromide; tetrabutylammonium tetrafluoroborate In N,N-dimethyl-formamide Ambient temperature; i = 250 mA, nickel-sponge cathode; | |
With (2,2'-bipyridine)nickel(II) dibromide; tetrabutylammomium bromide In N,N-dimethyl-formamide for 5h; other aryl and vinyl halides; other α-chloroester; electroreductive coupling; |
With [2,2]bipyridinyl; tetrabutylammomium bromide; nickel dibromide In N,N-dimethyl-formamide for 5h; electrochemical process; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 55% 2: 32% | With iodine trichloride; trimethyl orthoformate at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 60% 2: 39% | With iodine; trimethyl orthoformate at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 18% 2: 63% | With lead(IV) acetate In various solvent(s) at 25℃; for 30h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sodium hydroxide; Pseudomonas fluorescens MTCCB0015 cell-free extract In phosphate buffer at 37℃; for 26h; | |
90% | With potassium hydroxide In ethanol at 20℃; | |
75% | With hydrogenchloride; sodium hydroxide 1.) reflux; |
75% | With hydrogenchloride; sodium hydroxide | |
With sodium hydroxide Yield given; | ||
pig liver esterase; | ||
With sodium hydroxide Yield given; | ||
With sodium hydroxide In methanol; water for 6h; Ambient temperature; Yield given; | ||
With sodium hydroxide In methanol for 4h; Heating; Yield given; | ||
With water Yield given; | ||
With sodium hydroxide at 80 - 85℃; for 3h; | ||
With sodium hydroxide In water Heating; Yield given; | ||
0.64 g | Stage #1: 2-phenylpropionic acid methyl ester With sodium hydroxide In water at 20℃; Stage #2: With hydrogenchloride In water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium hexamethyldisilazane; N-Fluoro-o-benzenedisulfonimide In tetrahydrofuran 1.) -78 deg C, 10 min; -78 to 0 deg C, 0.5 h, 2.) r.t., 2 h; | |
With fluorinated heterocycle (62); lithium diisopropyl amide 1.)THF, 2.)-78 deg C -> r.t.; Yield given. Multistep reaction; | ||
Multi-step reaction with 2 steps 1: (i-Pr)2NH, BuLi / tetrahydrofuran; pentane / 0.5 h / -10 °C 2: 55 percent / N-fluorosultam / tetrahydrofuran / -78 deg C, 1 h, r.t., 1 h |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.87% | With N-Bromosuccinimide; Perbenzoic acid In tetrachloromethane at 70℃; | B Step B: methyl 2-bromo-2-phenylpropanoate A mixture of methyl 2-phenylpropanoate (5.22 g, 31.83 mmol) , NBS (6.80 g, 38.19 mmol) , BPO (0.385 g, 1.591 mmol) in carbon tetrachloride (20 mL) was stirred at 70 overnight. The mixture was concentrated, the residue was washed with PE and filtered, the filtrate was concentrated to give methyl 2-bromo-2-phenylpropanoate (7.57 g, 97.87%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.5 Hz, 2H) , 7.40 -7.27 (m, 3H) , 3.80 (s, 3H) , 2.30 (s, 3H) |
97.87% | With N-Bromosuccinimide; dibenzoyl peroxide In tetrachloromethane at 70℃; | B Step B: methyl 2-bromo-2-phenylpropanoate A mixture of methyl 2-phenylpropanoate (5.22 g, 31.83 mmol) , NBS (6.80 g, 38.19 mmol) , BPO (0.385 g, 1.591 mmol) in carbon tetrachloride (20 mL) was stirred at 70 C overnight. The mixture was concentrated, the residue was washed with PE and filtered, the filtrate was concentrated to give methyl 2-bromo-2-phenylpropanoate (7.57 g, 97.87%) as yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.55 (d, J = 7.5 Hz, 2H) , 7.40 -7.27 (m, 3H) , 3.80 (s, 3H) , 2.30 (s, 3H) |
67% | Stage #1: 2-phenylpropionic acid methyl ester With n-butyllithium; diisopropylamine In tetrahydrofuran; hexane at -78℃; Inert atmosphere; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran; hexane at 20℃; for 2h; Inert atmosphere; Stage #3: With N-Bromosuccinimide In tetrahydrofuran; hexane at -78 - 20℃; for 2h; Inert atmosphere; |
60% | With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile); Methyl formate Irradiation; Reflux; | |
With N-Bromosuccinimide In tetrachloromethane | ||
With N-Bromosuccinimide In tetrachloromethane for 0.75h; Photolysis; | ||
With N-Bromosuccinimide; dibenzoyl peroxide In cyclohexane; water at 50℃; for 4h; Inert atmosphere; | 2.b b) Methyl 2-bromo-2-phenylpropanoate; Methyl 2-phenylpropanoate in a solution in cyclohexane (prepared in step a) (22.42g; based on 100% yield from step a) was charged to a reaction vessel. Hydrobromic acid (48%, 0.62mL) was then charged followed by cyclohexane (22.4mL) as a line wash. Dibenzoyl peroxide (75%, 2.2Ig) and N-bromosuccinimide (31.6Ig) were then charged to the vessel and the reaction heated to 500C (+/-3°C) and stirred at this temperature for at least 4hrs. The reaction was monitored by GC analyzing the methyl 2-bromo-2- phenylpropanoate : methyl 2-phenylpropanoate ratio (specification >;96:4). Upon completion the reaction mixture was cooled to 200C (+/-3°C). The reaction mixture was filtered to remove the solid succinimide by-product, washing the filter cake twice with cyclohexane (22.4mL). The solid by-product was discarded. NaHSO3 (aq) (10%w/w, 81.9mL) was then charged and stirred for 15mins before allowing the phases to separate discarding the lower aqueous phase. Water (81.9mL,) was then charged and stirred for 15mins before allowing the phases to separate discarding the lower aqueous phase. 3- Pentanone (201.9mL) was then charged and the mixture was distilled at 45°C, 150- 280mbar removing 21OmL of solvent. The reaction mixture was cooled to 23°C (+/-3°C). 3- Pentanone (10 ImL) was then charged and the solvent composition analyzed by GC (specification | |
With N-Bromosuccinimide In tetrachloromethane for 4h; Reflux; Inert atmosphere; | 1.B A carbon tetrachloride (150 mL) solution of the intermediate from Step A (10.39 g, 66.6 mmol), N-bromosuccinimide (14.22 g, 80 mmol) and AIBN (0.547 g, 3.33 mmol) was heated to reflux. After 4 hours the reaction solution was cooled to room temperature and the mixture filtered. The filtrate was concentrated and the residue purified by silica gel chromatography using a hexanes/EtOAc gradient to give the indicated product. NMR (500 MHz, CHCh -d): δ 7.59- 7.53 (m, 2H); 7.37-7.30 (m, 3H); 3.80 (s, 3H); 2.31 (s, 3H). | |
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane for 4h; Reflux; | 2.B Step B: Methyl 2-bromo-2-phenylpropanoate. A carbon tetrachloride (150 mL) solution of the intermediate from Step A (10.39 g, 66.6 mmol), NBS (14.22 g, 80 mmol) and AIBN (0.547 g, 3.33 mmol) was heated to reflux. After 4 h the reaction solution was cooled to RT and the mixture filtered. The filtrate was concentrated and the residue purified by silica gel chromatography using a 10% to 50% EtOAc in hexanes gradient to give the title product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89.5% | With sodium hypochlorite In acetic acid; acetone at 0℃; for 10h; | |
65% | With [bis(acetoxy)iodo]benzene; water; lithium bromide at 20℃; for 0.25h; | |
56% | With tetraethylammonium bromide; water; 1-hydroxy-3H-benz[d][1,2]iodoxole-1,3-dione at 65℃; for 2.5h; |
Multi-step reaction with 2 steps 1: 88 percent / trityl perchlorate / CH2Cl2 / 0.08 h / 0 °C 2: 87 percent / methanol; various solvent(s) / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With diethylamino-sulfur trifluoride In dichloromethane at 25℃; for 2h; | |
74% | With diethylamino-sulfur trifluoride In dichloromethane at 25℃; for 2h; further 1-aryl-1,1-dimethoxypropan-2-ols; | |
55% | With pyridine; sulfuryl dichloride In dichloromethane at -50℃; for 3h; |
55% | With pyridine; sulfuryl dichloride In dichloromethane at -50℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With mercury dichloride; mercury(II) oxide In methanol; water for 5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 90% 2: 10% | With 3-chloro-benzenecarboperoxoic acid In methanol at 25℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene at 115℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | In methanol at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With lithium perchlorate; methyl iodide Ambient temperature; anodic oxidation at constant current; | |
99% | With sulfuric acid; N-methyl-N-[3-(4-diacetoxyiodo)phenoxy-1-propyl]pyrrolidinium 4-methylbenzenesulfonate at 60℃; for 3h; Inert atmosphere; | |
98% | With trifluorormethanesulfonic acid; [bis(acetoxy)iodo]benzene In methanol; Cyclooctan at 50℃; for 0.0335h; |
94% | With sulfuric acid; thiophen-3-yl-λ3-iodanediyl diacetate at 60℃; for 2h; | |
91% | With 4-bromo-4'-(diacetoxyiodo)biphenyl; sulfuric acid at 60℃; for 2h; | |
85% | With [bis(acetoxy)iodo]benzene; sulfuric acid at 60℃; for 2h; | |
85% | With [bis(acetoxy)iodo]benzene; sulfuric acid at 60℃; for 2h; | |
85% | With poly[4-(diacetoxyiodo)styrene]; sulfuric acid In acetonitrile at 60℃; for 0.5h; | |
81% | With [bis(acetoxy)iodo]benzene; sulfuric acid at 60℃; for 0.166667h; | |
81% | With [bis(acetoxy)iodo]benzene; sulfuric acid at 60℃; for 0.166667h; | |
80% | With poly[4-(diacetoxyiodo)styrene]; sulfuric acid at 60℃; for 0.166667h; | |
78% | With iodosylbenzene; sulfuric acid for 10h; Ambient temperature; | |
70% | With lead(IV) acetate; perchloric acid at 50℃; for 2h; | |
70% | With lead(IV) acetate at 50℃; for 2h; | |
62% | With trifluorormethanesulfonic acid; [bis(acetoxy)iodo]benzene at 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 62% 2: 26% | With iodine trichloride; trimethyl orthoformate at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 66% 2: 24% | With iodine; trimethyl orthoformate at 23℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 3 % Chromat. 2: 80% | With hydrogenchloride; triphenylphosphine In benzene at 125℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With samarium diiodide; water; triethylamine In tetrahydrofuran at 20℃; for 24h; Inert atmosphere; | |
94.8% | With lithium aluminium tetrahydride In diethyl ether for 1.16667h; Ambient temperature; | |
Multi-step reaction with 2 steps 1: diisobutylaluminium hydride / toluene; pentane / 0.5 h 2: 2,4,6-tri-t-butylphenol, 1 M trimethylaluminium / hexane; pentane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In water monomer; toluene at 90℃; for 24h; Inert atmosphere; Schlenk technique; Autoclave; | 4.2 Catalysis experiment General procedure: The catalytic reaction was carried out in 35mL stainless steel autoclave fitted with pressure gauze. A typical experiment involved the addition of catalyst 2a (10.7mg, 0.02mmol), PPh3 (10.5mg, 0.04mmol), 1-hexene (0.5mL, 4mmol), 32% HCl (20μL, 0.2mmol), methanol (3mL) and toluene (5mL) to the reactor. The reactor was then degassed and pressurized with CO (5MPa) at room temperature. The reaction mixture was heated to 90°C and stirred for 24h. At the end of the reaction time, the reactor was cooled, excess CO was vented off and reaction mixture was analyzed using GC and GC-MS to determine the percentage conversion of the alkene to esters. GC analyses were performed on a Varian series CP-3900 equipped with a capillary column (Wcot Fused Silica 50m×21mm CP SIL PONA CB DF=0.5UM) and a flame ionization detector (FID). GC-MS analyses were performed on a Shimadzu GC-MS-QP2010 fitted with a quadrupole mass detector. |
76% | With 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate; α,α'-bis(di-t-butylphosphino)-o-xylene; Palladium(0) bis(dibenzylideneacetone) In dichloromethane at 20℃; for 14h; regioselective reaction; | |
66% | With 5-chloro-2-hydroxybenzoic acid; Orthoboric acid; Tri(p-tolyl)phosphine for 24h; Heating; |
1: 55 % Chromat. 2: 45% | With Pd(2-OCOC5H4N)(PPh3)OTs; toluene-4-sulfonic acid In water monomer at 75℃; for 1.6h; | |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) In 1,4-dioxane at 110℃; for 4h; effect of solvent, effect of CoCl2 additive; | ||
With stannous chloride In toluene at 60 - 100℃; Yield given. Yields of byproduct given; | ||
With bis(benzonitrile)palladium(II) chloride; (R,R)-1-Ph2P-2,1'-[(1-(chex)2P-)-1,3-propanediyl]ferrocene In toluene at 90℃; for 168000h; | ||
With toluene-4-sulfonic acid; triphenylphosphine In toluene at 115℃; for 22h; | ||
With dicyclohexylphenylphosphine In propan-2-one at 50℃; for 50h; | ||
1: 60 % Spectr. 2: 16 % Spectr. | With [C4mim][NTf2]; triphenylphosphine at 90℃; for 3h; | |
With methanesulfonic acid; α,α'-bis(di-t-butylphosphino)-o-xylene at 20℃; for 17h; | ||
With triphenylphosphine at 80℃; for 16h; Title compound not separated from byproducts.; | ||
Stage #1: styrene; methanol With tetraethylsilane; 1-Methylnaphthalene Sealed vial; Inert atmosphere; Stage #2: carbon monoxide at 25℃; Autoclave; Inert atmosphere; | 15 Example 15: Methoxycarbonylation of styrene using [Pd2(Xyl-Phanephos)CI4] as catalyst at room temperature.Lithium chloride (8.4 mg, 0.20 mmol), para-toluenesulfonic acid (34.4 mg, 0.20 mmol) and [(Xyl-(S)-Phanephos)Pd2CI4] (0.01 mmol) were weighed into a 5 ml microwave vial. A stirring bar was added and the vial was sealed with a crimp cap and put under inert atmosphere. Styrene (1 mmol), dry and degassed methanol (1.5 ml) and an internal standard (approximately 10μΙ of either tetraethylsilane and 1-methylnaphtalene) were added using a syringe. The solution was mixed before 20 μΙ of the solution was diluted in CDCI3 and analysed using NMR (to give a to spectra that calibrates the internal standard against starting material). The caps were pierced with two needles and quickly placed in an autoclave that had previously been placed under an argon atmosphere before being opened under a flow of argon. The autoclave was sealed, purged three times with CO and then pressurised to 30 bar and heated in a preheated oil bath at 25 °C with constant magnetic stirring. After the desired time, the autoclave was cooled to room temperature and the pressure released slowly. The mixture was then analysed by taking a sample, diluting with CDCI3 and obtaining a 1H NMR spectrum. The solvent was carefully removed from the reaction mixture and the crude product was filtered through a small column packed with Si02 eluting with hexane: ethylacetate 8:1. The solvent was removed to give carboxylic acid ester product as a 47:53 mixture of branched and linear isomers (71 % conversion to ester, 62 % isolated yield). The ratio of optical isomers was 94.5:5.5.The enantiomeric excess was determined by HPLC, using a Chirapak AD-H, 250 x 4.6 mm, 5 pm with guard cartridge, n-hexane 100%, 0.5 mL min"1, 210 nm, iR[(+)-S] = 1 .9 min, fR[(-)-R] = 20.0 min, rR[linear] = 25.1 min. GCMS shows the expected linear and branched esters. EIMS 164 (M+).NMR data for catalysis products: Methyl-2-phenylpropanoate:1H NMR (300 MHz, CDCI3) δ 1.42 (d, J = 9, CH3, 3H), 3.57 (s, CH3, 3H), 3.65 (q, J = 9 Hz, CH, 1 H), 7.07- 7.28 (m, ArH, 5H). 13C NMR (75 MHz, CDCI3) δ 18.6, 45.5, 52.1 , 127.2, 127.5, 128.7, 140.5, 175.1.Methyl-3-phenylpropanoate: NMR (300 MHz, CDCI3) δ 2.55 ( t, J = 7.5, CH2, 2H ), 2.87 (t, J = 7.5, CH2, 2H), 3.58 (s, OCH3, 3H), 7.07-7.28 (m, ArH, 5H). 13C NMR (75 MHz, CDCI3) δ 31.0, 35.7, 51.7, 126.3, 128.3, 128.5, 173.4. | |
With trifluromethanesulfonate[bis(1-naphthyl)diphenylphosphine]palladium(II); toluene-4-sulfonic acid In 1,2-dichloro-ethane at 75℃; for 6h; Inert atmosphere; High pressure; chemoselective reaction; | ||
With toluene-4-sulfonic acid; triphenylphosphine; palladium (II) chloride In toluene at 125℃; High pressure; Inert atmosphere; regioselective reaction; | 2.1 Catalytic Reactions and Kinetic Study The catalytic reactions including those corresponding to the kinetic study were carried out in a high pressure reactor (125 mL), supplied by Parr Instruments (model 4561), which was provided with arrangements for sampling of liquid contents, automatic temperature and pressure control as well as variable stirring speed. In a typical run, a solution of PdCl2, the corresponding equivalents of triphenylphosphine and TSA, the substrate, the alcohol, isooctane (7.5 mmol) as the internal standard and toluene were added to the reactor. The solution was carefully deoxygenated with argon, and the reactor charged with CO (5-50 atm) and heated to a pre-set temperature. At the end of the reaction, the catalytic mixtures were analyzed by gas chromatography, using a 3300 Series VARIAN instrument fitted with a flame ionization detector (FID) and a 2 m20 % SP-2100 on a 0.1 % carbowax 100/120 Supelcoportcolumn, using N2 as carrier gas. Products were quantified with a microcomputer coupled to Measurement Computing interphase using the Cromat 1.2 software; the organic products were additionally identified by GC/MS HP5890/5971 coupled system using a Quadrex PONA 5 % phenyl methyl silicone, 25 m, 320 μm column. Each reaction was repeated at least twice in order to assure there producibility of the results. Statistical studies were performed using analysis of variance (ANOVA) to test the difference between means. Significant differences were considered when P0.05. | |
1: 27 %Spectr. 2: 73 %Spectr. | With titanium isopropoxide; lithium chloride; palladium (II) chloride; 1,3,5,7-tetramethyl-2,4,8-trioxa-6-phenyl-6-phosphaadamantane In 1,2-dimethoxyethane at 110℃; for 22h; Autoclave; Overall yield = 75 %; regioselective reaction; | |
With hydrogenchloride; C34H33N3OPPd(1+)*C32H12BF24(1-); triphenylphosphine In toluene at 90℃; for 24h; Autoclave; regioselective reaction; | General procedure for the methoxycarbonylation reactions General procedure: The catalytic methoxycarbonylation reactions were performed in a stainless steel autoclave equipped with temperature control unit and a sample valve. In a typical experiment, complex 4 (48.78mg, 0.08mmol), PPh3 (0.04g, 0.16mmol), HCl (0.03mL, 0.80mmol) and 1-hexene (2mL, 15.93mmol) were dissolved in a mixture of methanol (20mL) and toluene (40mL). The reactor was evacuated and the catalytic solution was introduced to the reactor via a cannula. The reactor was purged three times with CO, set at the required pressure and temperature and the reaction stirred at 500 rpm. At the end of the reaction time, the reaction was cooled, excess CO was vented off and the samples drawn for GC analysis to determine the percentage conversion of the alkene substrate to esters. GC-MS analyses were run under the following standard chromatography conditions: -25m CPSil 19 capillary column, 1.2 mm film thickness, Helium carrier column gas 5psi, injector temperature 250 °C, oven program 50 °C for 4 min rising to 200 °C at 20 °C/min and holding at 200 °C. The branched and linear esters were assigned using standard authentic samples. | |
With aluminium trifluoromethanesulphonate; palladium diacetate; triphenylphosphine In 5,5-dimethyl-1,3-cyclohexadiene at 95℃; for 0.416667h; Overall yield = 87 %; regioselective reaction; | Methoxycarbonylation of Alkenes 1-4, 9-15, 30 and 34-39; General Procedure General procedure: Al(OTf)3 (10 mol%), Ph3P (20 mol%), xylene (0.5 g), and the appropriate alkene (4 mmol) were added together in the Parr reactor and dissolved in MeOH (6 mL). The reactor was degassed and allowed to heat up to 95 °C. Pd(OAc)2 (5 mol%) dissolved in MeOH (2 mL) was injected, whereafter the pressure was set to 35 bar of CO. Conversions, yields, and product ratios were determined utilizing a Shimadzu 2010 GC instrument with xylene as the internal standard (Tables 2-4). Where applicable, the products were directly purified by flash column chromatography [100 g Merck Kieselgel 60 (230-400 mesh) per gram of crude mixture] with the eluent as indicated. | |
With palladium diacetate; toluene-4-sulfonic acid; bis[2-(diphenylphosphino)phenyl] ether In toluene at 130℃; for 18h; Autoclave; Overall yield = > 99 percentChromat.; regioselective reaction; | ||
With mesitylene sulfonic acid; bis(2-(diphenylphosphino)naphthyl)methane; palladium (II) 2,4-pentanedionate at 80℃; for 12h; Autoclave; | 23.2 Preparation of Methyl Phenylpropionate/2-Methyl Phenyl Acetate: In a 100-mL autoclave, add Pd(acac) 2 (0.08 mmol) and aryl bidentate phosphine ligand m (0.04) mmol), 2,4,6-trimethylbenzenesulfonic acid (0.1 mmol), styrene (30 mmol), anhydrous methanol (10 mL). After the reactor was sealed, the reactor was replaced with carbon monoxide three times, and then carbon monoxide was charged until the reactor pressure was 6.0 MPa. The temperature was slowly raised to 80°C by a temperature controller and reacted for 12 hours. After cooling to room temperature, slowly deflate, unload the kettle, the liquid obtained by the reaction was qualitatively analyzed by Agilent 6890/5973 gas chromatography-mass spectrometry, and quantitatively analyzed by HP-7890A gas chromatography, using biphenyl as the internal standard, benzene The conversion rate of ethylene is 90%, the selectivity of the hydroesterification products (methyl phenylpropionate, methyl 2-methylphenylacetate) is 95%, and the methyl phenylpropionate/2-methylphenylacetate is 96 /4. The reaction formula is as follows: | |
With platinum(II) bis(acetylacetonate); C28H36P2; toluene-4-sulfonic acid at 120℃; for 20h; Sealed tube; Inert atmosphere; Autoclave; Overall yield = 95 percent; | ||
With hydrogenchloride; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); toluene-4-sulfonic acid; triphenylphosphine In water monomer at 75℃; for 24h; Autoclave; regioselective reaction; | ||
With aluminium trifluoromethanesulphonate; o-dimethylbenzene; palladium diacetate; triphenylphosphine at 95℃; for 0.5h; Autoclave; Overall yield = 93 percentChromat.; | Autoclave procedure. General procedure: Pd(OAc)2 (5 mol%), Al(OTf)3 (10 mol%), PPh3 (20 mol%), xylene (0.5 g) and the alkene (4 mmol) were added together in the Parr autoclave reactor and dissolved in MeOH (8 ml). The mechanical stirrer was activated, the reactor purged with CO (purified by passing the gas through a CrO3 column) and allowed to heat up to 95 °C, where after it was pressurized to 12 bar with CO. | |
With toluene-4-sulfonic acid at 90℃; for 3.5h; Autoclave; | ||
With (R)-(+)-(N-2-pyridylmethylidene-1-phenylethylamine)palladium(II)dichloride; toluene-4-sulfonic acid; triphenylphosphine In methanol; toluene at 90℃; for 24h; Overall yield = 63 percent; | 3.4. General procedure for the methoxycarbonylation reactions The catalytic methoxycarbonylation reactions were performedin a stainless-steel autoclave equipped with a temperature controlunit and a sample valve. In an experiment the Pd complex, PPh3,PTSA and styrene (1:2:10:200) were dissolved in a mixture ofmethanol and toluene. The reactor was evacuated, and the catalyticsolution was introduced to the reactor via a cannula. The reactorwas purged three times with CO, and then set at the required pressure,heated to the desired temperature and the reaction stirred at500 rpm. At the end of the reaction time, the reaction was cooled,excess CO was vented off and samples drawn for GC analysis todetermine the percentage yields. | |
With (E)-N-(6-methylpyridin-2-yl)-N'-phenylbenzimidamide palladium(II); toluene-4-sulfonic acid; triphenylphosphine In toluene at 100℃; for 24h; Autoclave; Schlenk technique; Overall yield = 99 percentChromat.; | ||
With Pd(II) diphosphine complex encapsulated into imine-linked covalent organic framework In 1,2-dichloro-ethane at 120℃; for 26h; Inert atmosphere; Glovebox; Autoclave; Overall yield = 88.4 percentChromat.; | ||
With tris(2-diphenylphosphinophenyl)phosphine; palladium diacetate; toluene-4-sulfonic acid In tetrahydrofuran at 140℃; for 4h; Autoclave; Overall yield = 91 percent; | 25-34 General procedure: Specific experimental steps: 0.01 mmol catalyst precursor, 0.012 mmol ligand, 0.012 mmol ligand, 0.05 mmol of p-toluenesulfonic acid, styrene 20 mmol, methanol 20 mL and THF 40 mL were added to the 200 mL of PTFE lining. The inner liner is placed in a high-pressure reactor, the airtightness of the device is tested after sealing, and the air in the reactor is replaced with carbon monoxide. Carbon monoxide gas is then fed and charged to 3.0MPa, reacting at 140 °C in a constant temperature heating sleeve for 4 h, cooling to room temperature and then slowly depressurizing. The conversion rate of styrene and the selectivity and yield of the product were calculated by GC-MS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 80.6% 2: 16.1% 3: 1.2% | With p-Ts; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; effect of the amount of p-Ts on carbonylation reaction; also further substrate investigated; | |
1: 16.1% 2: 1.2% 3: 80.6% | With p-Ts; triphenylphosphine In 1,4-dioxane at 100℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In water at 180℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 160℃; for 0.2h; microwave irradiation; | |
98% | With 1,8-diazabicyclo[5.4.0]undec-7-ene for 5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With hydrogen In methanol at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 8h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With tri-tert-butyl phosphine; lithium dicyclohexylamide In toluene at 20℃; for 15h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: 2-phenylpropionic acid methyl ester With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 2.66667h; Stage #2: With hydrogen chloride In tetrahydrofuran; hexane; water-d2 at 20℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In toluene at 100℃; for 70h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen In toluene at 30℃; for 90h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 1,4-dioxane at 109.85℃; for 2h; | ||
With toluene-4-sulfonic acid; triphenylphosphine In 1,2-dichloro-ethane at 75℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sulfuric acid; iodic acid; trimethyl orthoformate at 65℃; | |
72% | With sulfuric acid; trimethyl orthoformate for 0.333333h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydride at 50℃; | EXAMPLE 10 Step c 2-Methyl-2-phenylpropionate, Methyl Ester EXAMPLE 10 Step c 2-Methyl-2-phenylpropionate, Methyl Ester Equip a two liter, 3-necked, round bottom flask with a thermowell with a thermometer, heating mantle, mechanical agitator, gas inlet for MeCl, rubber septum for sampling by syringe and a cryoscopic condensing system. The condensing system is composed of an 18 inch inner helical coil/outer jacket condenser chilled to -50 C. with refrigerated acetone topped with a dry ice cold finger having approximately 100 square inches of chilled surface area. The cold finder is vented through a drying tube filled with drying agent and MeCl is supplied from a lecture bottle mounted on a digital balance. The feed rate can be accurately controlled using a needle valve and monitored by rotomter. The rotometer is calibrated with MeCl to give an average response of 2.5 mg/min/scale division. Phenylacetic acid, ethyl ester is supplied via {fraction (1/16)} inch stainless steel tubing inserted through the rubber sampling septum by a HPLC pump from a 1 liter bottle mounted on a digital balance. The bottle is sealed with a septum and vented through a drying tube filled with drying agent. The temperature is controlled using a thermowatch to regulate the heating mantle. If cooling is required, it is accomplished either by immersing the reaction flask in a water bath or simply by removing the mantle. The phenylacetic acid, ethyl ester pump is primed with phenylacetic acid containing 1 st % t-butanol and the phenylacetic acid, ethyl ester balance is zeroed. The MeCl balance is zoned and a 200 g sample of 60% NaH is weighed into a wide mouth plastic jar in a nitrogen filled glove bag and is transferred to the reaction vessel through a funnel (sampling septum is removed). Through the same funnel is added anhydrous glyme (800 mL) and the septum (pierced by the {fraction (1/16)} inch phenylacetic acid, ethyl ester feed tube) is replaced. The mixture is agitated and heated to 50 C. while MeCl (40 g) is introduced. When the reaction mixture reaches 50 C., the continuous addition of phenylactic acid, ethyl ester/t-butanol at 1 mL/min and MeCl at approximately 0.62 g/min. is initiated. Samples of about p.1 mL are withdrawn at intervals using a disposable syringe fitted with an 8 inch needle. A portion of the sample (5-15 drops depending on the accumulation of product) is dissovled in 25% aqueous acetonitrile (5 mL) and analyzed immediately. The reaction is continued for an additional 2 hours at 50 C. and then at ambient temperature overnight. In the apparatus described above, agitate NaH (180 g of 60%) and anhydrous glyme (800 mL) and heat to 50 C. Add MeCl (52 g) along with methyl phenylacetate (20 g). Stir for 1 hour at 50 C., then add, by continuous addition, methyl phenylacetate (0.8 mL/min) and MeCl (approximately 0.53 g/min). Stir for 1 hour, stop the additoina and continue heating for 1.5 hours. Resume the additions and run for 45 minutes. Allow to agitate at ambient temperature overnight. Heat the reaction to 50 C. and resume the addition of methyl phenylacetate (0.4 mL/min) and MeCl (approximately 0.27 g/min). When a total of 246 g of methyl phenylacitate has been added, stop the addition and agitate overnight. Distill the glyme at 1 atm. until the pot temperature reaches 125 C. Cool the residue and pour into water (1 L) containing acetic acid (100 mL). Filter through filter aid and separate the phases. Distill the organic phase through a 10-plate Oldershaw column fitted with a reflux splitting head at 4 mm Hg. Collect 10 mL at a 5:2 reflux ratio and discard. Collect the title compound at a 2:1 reflux ratio and head temperature of 93 C. (100 g). | |
Stage #1: benzeneacetic acid methyl ester With n-butyllithium; N-ethyl-N,N-diisopropylamine In tetrahydrofuran; hexane at -78℃; for 0.333333h; Inert atmosphere; Stage #2: methylene chloride In tetrahydrofuran; hexane at -78 - 0℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanolic hydrochloric acid | 1.a a. a. methyl 2-phenylpropionate 50 g (0.3 mol) of 2-phenylpropionic acid are dissolved in 375 ml of methanolic hydrochloric acid and stirred for 14 hours at ambient temperature. The solvent is removed and the residue extracted with ethyl acetate and saturated sodium hydrogen carbonate solution. The organic phases are extracted with water and saturated saline solution, dried over magnesium sulphate and concentrated by evaporation. Yield: 51 g (94.8% of theory). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | 8 α-Phenylpropionic acid The product, methyl α-phenylpropionate, is hydrolyzed to α-phenylpropionic acid according to the procedure of example 5. Yield 85%. α-Phenylmethylpropionate can be obtained under similar conditions, by reacting a mixture of phenylacetic acid, dimethyl carbonate and K2 CO3, in a 1:20:2 molar ratio, in autoclave at a temperature of 225° C., for 15 hours. | |
85% | 8 α-Phenylpropionic acid The product, methyl α-phenylpropionate, is hydrolyzed to α-phenylpropionic acid according to the procedure of example 5. Yield 85%. α-Phenylmethylpropionate can be obtained under similar conditions, by reacting a mixture of phenylacetic acid, dimethyl carbonate and K2CO3, in a 1:20:2 molar ratio, in autoclave at a temperature of 225°C, for 15 hours. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol | 1 (1) (1) Methyl 2-phenylpropionate 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2 SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~100 ml). The products were extracted with Et2 O (150 ml*3), which was washed with saturated NaHCO3, H2 O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give methyl 2-phenylpropionate as a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg). | |
In methanol | A A. A. Methyl 2-phenylpropionate 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2 SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~30 ml), which was poured into ice water (~100 ml). The products were extracted with Et2 O (150 ml*3), which was washed with saturated NaHCO3, H2 O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg). | |
In methanol | 1.1 (1) (1) (+)-Methyl 2-phenylpropionate (+) 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2 SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~100 ml). The products were extracted with Et2 O (150 ml*3), which was washed with saturated NaHCO3, H2 O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give (+) methyl 2-phenylpropionate as a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg), [α]D =+111° (c=2, toluene). |
In methanol | 1.1 (1) (1) (+) Methyl 2-phenylpropionate (+) 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2 SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~100 ml). The products were extracted with Et2 O (150 ml*3), which was washed with saturated NaHCO3, H2 O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give (+) methyl 2-phenylpropionate as a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg), [α]D =+111° (c=2, toluene). | |
In methanol | 1 (1) (1) (+) Methyl 2-phenylpropionate (+) 2-Phenylpropionic acid (8.4 g, 56 mmol) in methanol (180 ml) and concentrated H2 SO4 (2 ml) were heated at reflux for 4 hours. The reaction was cooled down to room temperature and concentrated in vacuo (~100 ml). The products were extracted with Et2 O (150 ml*3), which was washed with saturated NaHCO3, H2 O and dried over MgSO4. Filtration and evaporation of solvent yielded a yellow oil (8.9 g), which was distilled to give (+) methyl 2-phenylpropionate as a colorless oil (8.34 g, 51 mmol, 91%, b.p. 73° C./1.5 mm Hg), [α]D =+111° (c=2, toluene). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In carbon disulfide | 5 EXAMPLE 5 EXAMPLE 5 Synthesis of methyl 2-[p-(trans-4-aminomethylcyclohexylcarbonyl)-phenyl]propionate [trans (125)], and 2-[p-(trans-4-aminomethylcyclohexylcarbonyl)phenyl]propionic acid hydrochloric acid [trans (111) hydrochloride]: Three grams of trans-4-aminomethylcyclohexanecarboxylic acid hydrochloride was suspended in 80 ml of carbon disulfide, and with vigorous stirring under ice cooling, 4.5 g of aluminum chloride was added. Then, a solution of 2.4 g of methyl 2-phenylpropionate in 30 ml of carbon disulfide was added, and the mixture was reacted for 3 hours under reflux. The reaction mixture was then worked up in the same way as in Example 4 to give 3.0 g (yield 71%) of trans (125) having the following properties. NMR (CDCl3, ppm): 7.85 (2H, d, J=8.5 Hz, benzene protons), 7.25 (2H, d, J=8.5 Hz, benzene protons), 3.65 (3H, s, --COOCH3), 3.8 STR26 1.5 (3H, d, --CH3), 0.9-3.0 (12H, m, protons of cyclohexane ring and --CH2 --). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In toluene at 80℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With n-butyllithium In tetrahydrofuran; hexane byproducts: LiOCH3; addn. of a soln. of butyllithium at 0 to -5°C, stirring at room temp. for 1 h, quenching with satd. aq. ammonium chloride soln.; extn. with diethyl ether and drying over MgSO4, evapn. of solvent, purifn. by flash column chromy., IR, NMR, elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
21% | In dichloromethane for 18h; Heating / reflux; | 59 Example 59 (Production of Amides) Under an argon atmosphere, a mixture of methyl phenylpropionate (3.0 mmol), benzylamine (3.6 mmol), Zn4(OCOCF3)6O (0.15 mmol) and methylene chloride (5mL) was heated under reflux for 18 hours, and as a result, N-benzyl-3-phenylpropanamide was obtained in 21% yield. The resulting compound was identified by comparison with physical property data of the known compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: methyl 2-hydroxy-2-phenylpropanoate With dmap; triethylamine; chlorophosphoric acid diphenyl ester In tetrahydrofuran at 45℃; Stage #2: With dichloro bis(acetonitrile) palladium(II); sodium tetrahydroborate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl In tetrahydrofuran; 1,2-dimethoxyethane at 75℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69 mg | With diisopropylamine In 1,2-dichloro-ethane at 60℃; for 4h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | In toluene at 80℃; for 1h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 24% 2: 11% | Stage #1: styrene; carbon monoxide With 1,1'-bis(diphenylphosphino)ferrocene; palladium diacetate; oxalic acid In 1,4-dioxane at 100℃; for 20h; Stage #2: diazomethyl-trimethyl-silane With methanol In 1,4-dioxane |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | Stage #1: styrene; carbon monoxide With hydrogenchloride; water; palladium diacetate; catacxium A In 1,4-dioxane at 100℃; for 20h; Stage #2: diazomethyl-trimethyl-silane With methanol In 1,4-dioxane regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | Stage #1: 2-phenylpropionic acid methyl ester With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: Cyclohexylmethyl bromide In tetrahydrofuran at 25℃; for 18h; | 41A A solution of 2-phenyl-propionic acid methyl ester (3.0 g, 18. 27 mmol) in tetrahydrofuran (25 mL) at-78 °C was treated dropwise with the lithium hexamethyldisilazide (21.9 mL, 1M in tetrahydrofuran, 21.9 mmol) and stirred for 1 hour. Bromomethyl-cyclohexane (3.09 mL, 21.92 mmol) was added to the reaction and the reaction was allowed to warm to 25 °C and stirred for 18 hours. The solvent was removed in vacuo and the residue was partitioned between water and ethyl acetate. The aqueous phase was extracted three times with ethyl acetate and the ethyl acetate layers were combined, dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with hexane, then 2.5% ethyl acetate in hexane, and 5% ethyl acetate in hexane to give the title compound (4.02 g, 84%). H NMR (300 MHZ, CDCL) : 8 PPM 1. 11 (M, 10 H) 1.55 (M, 4 H) 1.80 (M, 1 H) 2.04 (M, 1 H) 3.64 (M, 3 H) 7.29 (M, 5 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Example 51A methyl 3-CYCLOPENTYL-2-METHYL-2-PHENYLPROPANOATE A solution of lithium bis (trimethylsilyl) amide (1M in tetrahydrofuran, 3.04 mL, 3.04 mmol, 1 equiv) under a N2 atmosphere was cooled to 0 C and treated with a solution of methyl 2-phenylpropionate (0.500 g, 3.04 mmol, 1 equiv) in dry tetrahydrofuran (2 mL). The reaction was stirred at 0 C for 2 hrs, then cooled to-78 C and treated with hexamethylphosphoric triamide (0.4 mL) and <strong>[3814-30-0]bromomethylcyclopentane</strong> (0.745 g, 4.568 mmol, 1.5 equiv). Stirred the reaction at-78 C and allowed the bath to slowly warm to room temperature overnight. After 15 hrs, the reaction mixture was quenched with 10% aq NH4CL (50 mL) and extracted with ethyl acetate (100 mL). The organic extract was washed with H2O (50 mL) and brine, then dried OVER NA2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by SIO2 flash chromatography with 2: 3 dichloromethane/hexanes to give the product as colorless oil (1.38 g, 5.60 mmol, 92%). H NMR (300 MHz, DMSO-d6) : 8 ppm 0.90-1. 12 (M, 2 H) 1.32-1. 72 (M, 10 H) 1.97-2. 12 (m, 2 H) 3.58 (s, 3 H) 7.19-7. 35 (M, 5 H) ; MS (APCI+) m/z 247 (M+H) +. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: 2-phenylpropionic acid methyl ester With lithium hexamethyldisilazane In tetrahydrofuran at -40℃; Stage #2: neohexyliodide In tetrahydrofuran at -40 - 20℃; for 3h; | 11; 29 Methyl 2,5,5-trimethyl-2-phenylhexanoate Under nitrogen atmosphere, lithium bis(trimethylsilyl) amide solution 1M in THF (13.4 mmol, 1.1 eq)was added to a solution of intermediate 9 (12.18 mmol, 1 eq) in THF (50 ml) at -40° C. The stirring was applied at -40° C. until complete formation of anion. At -40° C., and under nitrogen atmosphere, intermediate 10 was slowly added, then the reaction mixture was warmed to room temperature, and stirred until complete disappearance of starting material (3 hours). The reaction was quenched with 1M aqueous hydrochloric acid, and extracted with MTBE. The organic layer was washed with aqueous saturated thiosulfate solution, water then dried on sodium sulphate. The solvent was removed under reduced pressure to give intermediate 11 (2.5 g, 85%), which was a brown oil. Intermediate 11 was characterized by the following spectroscopic data: 1H NMR (CDCl3, 400 MHz) δ (ppm) 0.81 (s, 9H), 0.98-1.03 (m, 2H), 1.47 (s, 3H), 1.80-1.87 (m, 1H), 3.60 (s, 3H), 7.16-7.21 (m, 1H), 7.24-7.27 (m, 4H).; Intermediate 292,5,5-trimethyl-2-phenyl-hexanoic acid methyl ester Under nitrogen atmosphere, lithium bis(trimethylsilyl) amide solution 1M in THF (13.4 mmol) was added to a solution of intermediate 27 (12.18 mmol) in THF (50 ml) at -40° C. The stirring was applied at -40° C. until complete formation of anion. At -40° C., and under nitrogen atmosphere, intermediate 10 was slowly added, then the reaction mixture was warmed to room temperature, and stirred until complete disappearance of starting material (3 hours). The reaction was quenched with 1M aqueous hydrochloric acid, and extracted with TBDME. The organic layer was washed with aqueous saturated thio sulfate solution, water then dried on sodium sulphate. The solvent was removed under reduced pressure to give intermediate 29, which was a brown oil. Intermediate 29 was characterized by the following spectroscopic data: 1H NMR (CDCl3, 400 MHz) δ (ppm) 0.81 (s, 9H), 0.98-1.03 (m, 2H), 1.47 (s, 3H), 1.80-1.87 (m, 1H), 3.60 (s, 3H), 7.16-7.21 (m, 1H), 7.24-7.27 (m, 4H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: hydratropic acid With 1,8-diazabicyclo[5.4.0]undec-7-ene In toluene at 20℃; for 1h; Stage #2: methyl iodide In toluene at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: 2-phenylpropionic acid methyl ester With lithium diisopropyl amide In tetrahydrofuran; ethylbenzene; toluene at -78℃; for 1h; Inert atmosphere; Stage #2: cyanomethyl bromide In tetrahydrofuran; ethylbenzene; toluene at -78℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | Stage #1: 2-phenylpropionic acid methyl ester With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.666667h; Stage #2: With 2-chloro-2-fluoro-2-phenylacetonitrile In tetrahydrofuran at -78℃; for 0.0833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84% 2: 8 %Spectr. | With indium (III) iodide; Dimethylphenylsilane In dichloromethane at 20℃; for 1.66667h; Inert atmosphere; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45.5% | With tetrabutyl ammonium fluoride In tetrahydrofuran at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With [(2)H6]acetone; potassium carbonate; 1-butyl-3-methylimidazolium chloride at 80℃; for 12h; | |
With water-d2; N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid at 37℃; for 48h; Enzymatic reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 60% 2: 10% | Stage #1: potassium dimethoxy(phenyl)(trifluoromethyl)borate With chloro-trimethyl-silane In 1,2-dimethoxyethane at -20 - -10℃; for 0.333333h; Inert atmosphere; Stage #2: ethyl diazoalaninate In 1,2-dimethoxyethane at -20 - 20℃; for 13h; Inert atmosphere; | General procedure for the reactions of borate 2a with diazo compounds 6. General procedure: TMSCl (140 μL, 1.1 mmol) or TMSOTf (200 μL, 1.1 mmol) was added to a solution of borate 2a (284 mg, 1.1 mmol) in 1,2-DME (1.5 mL) at -20 °C, and the temperature was allowed to warm to -10 °C over 20 min. The mixture was again cooled to -20 °C, diazo compound 6 (1 mmol) and MeOH (49 μL, 1.2 mmol) were added [in the case of ethyl diazopropionate (6d) the reaction was carried out without MeOH], and the temperature was allowed to warm to 0 °C over 1 h. The cooling bath was removed, and the mixture stirred at room temperature for the time indicated in Table 4. The work-up was the same as that used in the procedure with EDA. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; hexanes; benzene at 25℃; for 2h; Cooling with ice; Inert atmosphere; | 1.A Trimethylsilyl diazomethane (2.0M in hexanes, 40 mL, 80 mmol) was added dropwise to a solution of racemic 2-phenylpropionic acid (10.0 g, 66.6 mmol) in benzene (100 mL) and methanol (20 mL) cooled in an ice bath. After the addition was complete the reaction solution was stirred at room temperature for 2 hours. The solution was then concentrated to give the indicated product. m/z = 165.1 (M+H). | |
In methanol; hexane; benzene at 18 - 25℃; for 2h; Cooling with ice; | 2.A Step A: Methyl 2-phenylpropanoate. Trimethylsilyl diazomethane (2.0M in hexanes, 40 mL, 80 mmol) was added dropwise to a solution of racemic 2-phenylpropionic acid (10.0 g, 66.6 mmol) in benzene (100 mL) and MeOH (20 mL) cooled in an ice bath. After the addition was complete the reaction solution was stirred at RT for 2 h. The solution was then concentrated to give the title product. | |
In methanol; ethyl acetate at 30℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With indium (III) iodide; Dimethylphenylsilane In dichloromethane at 20℃; for 5h; optical yield given as %de; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | Stage #1: 2-phenylpropionic acid methyl ester With n-butyllithium; diisopropylamine; lithium diisopropyl amide In tetrahydrofuran; hexane at -78℃; for 1h; Stage #2: 1-Bromopentane In tetrahydrofuran; hexane at -78 - 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.4% | With 0.17percent Pd-P-OP/LSI-600 catalyst In toluene at 80℃; for 3.5h; Autoclave; | |
85% | With manganese(I) pentacarbonyl bromide; water monomer; C34H24N3P; palladium (II) chloride In toluene at 120℃; for 20h; regioselective reaction; | |
82% | With water monomer; palladium (II) chloride; 1-(2-methoxyphenyl)-2-(dicyclohexylphosphino)pyrrole In toluene at 100℃; for 20h; regioselective reaction; |
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); toluene-4-sulfonic acid In tetrahydrofuran at 120℃; for 24h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dodecacarbonyl-triangulo-triruthenium; 2-((dicyclohexylphosphino)methyl)-1-methyl-1H-imidazolin In N,N-dimethyl-formamide at 135℃; for 24h; Inert atmosphere; Overall yield = 71 %; regioselective reaction; | ||
1: 87.2 %Chromat. 2: 10.8 %Chromat. | With methanesulfonic acid; bis(acetylacetonato)palladium(II); 1,2-bis[di(t-butyl)phosphinomethyl]benzene In methanol at 100℃; for 20h; Autoclave; Inert atmosphere; Overall yield = 98 %Chromat.; | 22 A 100 ml stainless steel autoclave is charged with 27 mmol of styrene (3.1 ml), Pd(acac)2, 0.08 mol % (6.3 mg), 28.4mg of BuPoX, 10 ml of methyl formate, 10 ml of methanol and 20 jii ofmethanesulphonic acid under a protective gas (argon or nitrogen for example). The autoclave is heated to 1000 C., followed by stirring at that temperature for 20 h. The autoclave is subsequently cooled down to room temperature and the residual pressure is released. A 5 ml quantity of isooctane is added to the reaction solution as an internal standard and the mixture is analysed by gas chromatography. The yield of n-product, i.e. methyl 3-phenylpropionoate, is 87.2%. The yield of the branched product methyl 2-phenyl- propionate is 10.8%. The total yield of methyl esters is accordingly 98% with an n:iso ratio of 89:11. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In benzene-d6 at 20℃; for 0.166667h; Inert atmosphere; Glovebox; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; | Methyl 2-diazo-2-phenylacetate (2e) General procedure: (Step 1) A mixture of 4-bromophenylacetic acid (1.08 g, 5.0 mmol) and 95 wt.% sulfonic acid (0.28 mL) inmethanol (5.0 mL) was refluxed for 5 h. The resulting mixture was cooled to room temperature and diluted withsaturated aqueous sodium hydrogen carbonate. The mixture was extracted with ethyl acetate and the combinedextracts were washed with brine, dried over sodium sulfate, and concentrated to obtain methyl (4-bromophenyl)acetate (38) (1.13 g, 99% yield) as a colorless oil. The crude product was used without purification. (Step 2)10 A solution of 38 (1.12 g, 4.89 mmol) and p-toluenesulfonyl azide11 (1.16 g, 5.88 mmol) in acetonitrile(9.8 mL) was treated with DBU (1.10 mL, 7.36 mmol) at 0 °C and the mixture was stirred for overnight at roomtemperature. The resulting mixture was quenched with saturated aqueous ammonium chloride and extracted withethyl acetate. The combined extracts were washed with brine, dried over sodium sulfate, and concentrated. Theresidue was purified by chromatography on silica gel (n-hexane/ethyl acetate = 10/1 as the eluent) to afford 2a(1.22 g, 98% yield) as an orange solid. |
[ 157444-69-4 ]
Methyl 2-(4-(tert-butyl)phenyl)-2-methylpropanoate
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[ 157444-69-4 ]
Methyl 2-(4-(tert-butyl)phenyl)-2-methylpropanoate
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