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CAS No. : | 5368-81-0 | MDL No. : | MFCD00017193 |
Formula : | C9H10O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DUKYPQBGYRJVAN-UHFFFAOYSA-N |
M.W : | 166.17 | Pubchem ID : | 79332 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.22 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 44.21 |
TPSA : | 35.53 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | Yes |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -5.65 cm/s |
Log Po/w (iLOGP) : | 2.27 |
Log Po/w (XLOGP3) : | 2.35 |
Log Po/w (WLOGP) : | 1.48 |
Log Po/w (MLOGP) : | 1.64 |
Log Po/w (SILICOS-IT) : | 1.7 |
Consensus Log Po/w : | 1.89 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.52 |
Solubility : | 0.499 mg/ml ; 0.003 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.74 |
Solubility : | 0.305 mg/ml ; 0.00184 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.59 |
Solubility : | 0.424 mg/ml ; 0.00255 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.49 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | 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 |
---|---|---|
93% | With hydrazine hydrate monohydrate In ethanol for 7h; Reflux; | |
93% | With hydrazine hydrate monohydrate In ethanol; lithium hydroxide monohydrate at 80℃; for 24h; | |
90% | With hydrazine hydrate monohydrate In ethanol Reflux; | 1.1 Part 1- Synthesis of 3-Methoxybenzohydrazide To a solution of methyl 3-methoxybenzoate (5.0 g, 30.1 mmol, 1.00 equiv) in EtOH (50 mL) was added hydrazine hydrate (80%, 9.4 g, 150 mmol, 5.00 equiv). The reaction was refluxed overnight, then concentrated under vacuum. The residue solidified upon standing at rt. The solid was triturated with hexane (100 mL) and the resulting solid separated and dried to yield 4.5 g (90%) of the desired product as a white solid. |
86% | With hydrazine monohydrate In ethanol for 0.266667h; Reflux; Microwave irradiation; | |
85% | With hydrazine In methanol for 3h; Reflux; | |
With hydrazine hydrate monohydrate | ||
With hydrazine In ethanol for 12h; Heating; | ||
With hydrazine hydrate monohydrate | ||
With hydrazine In lithium hydroxide monohydrate at 60℃; | ||
With hydrazine hydrate monohydrate In ethanol at 70℃; for 3h; | ||
With hydrazine hydrate monohydrate In methanol Reflux; | ||
With hydrazine hydrate monohydrate In ethanol Reflux; | General procedure for the synthesis of the hydrazide ligands General procedure: Different substituted carboxylic acids (20 mmol) (A) were stirred with thionyl chloride (100 mmol) in dry methanol (75 ml) or 5-6 h to synthesize corresponding methyl esters (B) (Scheme1). After extraction of esters in chloroform, solvent was evaporated and esters (66 mmol) were refluxed with hydrazine hydrate(330 mmol) in ethanol (75 ml) for 4-5 h. A solid was obtained upon removal of the solvent by rotary evaporation. The resulting solid was washed with hexane to afford hydrazide ligand (C). The spectral and analytical data are given below. | |
With hydrazine hydrate monohydrate In methanol | ||
With hydrazine hydrate monohydrate In methanol for 5h; Reflux; | General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C. | |
With hydrazine hydrate monohydrate In ethanol Reflux; | ||
With hydrazine hydrate monohydrate | ||
With hydrazine hydrate monohydrate In methanol at 65 - 67℃; for 9h; | ||
With hydrazine hydrate monohydrate Cooling with ice; Reflux; | General procedure for synthesis of hydrazides (5a-l)1 General procedure: Carboxylic acids (10 mmol) were refluxed for 1-2 h in methanol (5 mL) in presence of conc. H2SO4 (catalytic amount) with continuous stirring. The reaction was monitored by TLC till the acids were fully converted to the corresponding esters [Eluent: EtOAc/Hexanes (1:4)]. The reaction mixture was allowed to cool down to room temperature and hydrazine monohydrate 80% (40 mmol, 1.91 mL) was added slowly in an ice bath. The reaction was then warmed to room temperature and refluxed for another 1-2 h and followed by TLC till formation of hydrazide. The reaction mixture was kept at refrigerator till the product precipitated. All hydrazides were isolated in quantitative yields and in a pure form. There melting points were in full agreement with the literature melting points of the same compounds. | |
With hydrazine hydrate monohydrate In methanol at 85℃; for 14h; | ||
With hydrazine hydrate monohydrate In methanol Reflux; Inert atmosphere; | 2.1.1. General procedure for the synthesis of hydrazides 2 General procedure: Hydrazine hydrate (5 mL, 40%) was added to a solution of requiredester (5.0 mmol) in methanol (20 mL). The solution was refluxed for12-24 h and monitored by TLC until starting material was completelyconsumed. After that, solvent was evaporated under reduced pressureand a small amount of water (5 mL) was added to precipitate the hydrazide,which was filtered and dried in vacuum to give a shiny white toyellow solid in excellent yields, without further purification. | |
With hydrazine hydrate monohydrate In methanol at 0 - 20℃; for 4h; | 4.3 General procedure for the synthesis of compounds 3a-3q General procedure: Compound 2a was dissolved in methanol and the mixture was cooled in an ice bath. Hydrazine hydrate (3 eq.) was added dropwise at 0°C. The resulting reaction mixture was stirred at room temperature for 4h. The reaction progress was monitored by TLC (MeOH/DCM=1:20) until it was completed. A crude solid 3a was obtained by filtering and washing with ice methanol, which was used to the next step without further purification. Preparation method of 3b∼3q was same as 3a. | |
With hydrazine hydrate monohydrate In ethanol Reflux; | Synthesis of benzohydrazide derivatives (4a-m) General procedure: Method A Methyl benzoate derivatives (2, 1 eq) and 85% hydrazine hydrate (10 eq) were dissolved in ethanol (45 mL). The mixture was refluxed overnight. After cooling, the solvent was removed in vacuo and the residue was separated on the Biotage SNAP Cartridge KP-Sil 100 g eluting with 0-60 % ethyl acetate/petroleum ether to afford compound 4. | |
With hydrazine monohydrate In methanol Reflux; | ||
With hydrazine hydrate monohydrate In ethanol at 90℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With pyridine; 4-dimethylaminopyridine In benzene | ||
In acetonitrile at 25℃; | ||
With triethylamine In dichloromethane at 0℃; | General procedure: Compounds 6a-t were synthesized from substituted benzoic acid via six steps according to the literature method as described. Various substituted benzoic acids 1a-t were treated with SOCl2 to give compounds 2a-t, which were reacted with CH3OH and EtN3 in CH2Cl2 at 0 to afford compounds 3a-t. Compounds 4a-t were prepared by the reaction of compounds 3a-t, hydrazine hydrate in CH3OH under reflux condition about 5h. Subsequently, compounds 5a-t were obtained by reaction of compounds 4a-t with CS2 and KOH in CH3OH. Compounds 6a-t were obtained by the cyclization reaction of compounds 5a-t in the presence of HCl at 0-5°C. |
With potassium carbonate at 65℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide | ||
With potassium carbonate | ||
With potassium carbonate In acetone for 12h; Heating; |
With potassium carbonate In acetone | ||
With potassium carbonate In acetone Reflux; | Synthesis of 5. 3-Hydroxybenzoic acid (Acros) (1.38 g) was dissolved in acetone (40 mL), then K2CO3 (3.0 g) and dimethyl sulfate (2.7 g) were added in one portion. The mixture was heated to reflux under stirring for 1-2 hours until 3-hydroxybenzoic acid was completely consumed to form 4 (monitored by TLC). Then the reaction mixture was cooled down to room temperature, and filtered through a short pad of silica gel to remove K2CO3. The resulting solid residue was washed with acetone (200 mL). The clear filtration was concentrated under vacuum to give a syrup-like residue, which was dissolved in 15 mL HNO3 (68-70% in aqueous as received) at room temperature. The solution was well stirred overnight until the starting material was consumed (monitored by TLC). Compound 5 was precipitated out from the solution (nitration by-products 5a and 5b were still in the solution and were recovered by extraction with CH2Cl2). Simple filtration will afford 5, which was recrystallized from MeOH or EtOAc/Hexane to give large colorless square crystals as pure product in about 50-60% yield. 1H NMR (300 MHz, CDCl3): 7.58 (1H, dd, J=1.2 Hz, J=7.2 Hz), 7.47 (1H, tri, J=8.1 Hz), 7.24 (1H, dd, J=1.2 Hz, J=8.1 Hz), 3.90 (3H, s), 3.87 (3H, s). 13C NMR (75 MHz, CDCl3): 163.4, 150.9, 130.8, 123.6, 122.1, 117.1, 56.8, 52.9. | |
With potassium carbonate In acetone Reflux; | 3-hydroxybenzoic acid (Acros) 4 (1.38 g) was dissolved in 40 mL acetone, then K2CO3 (3.0 g) and dimethyl sulfate (2.7g) were added in one portion. The mixture was heated to reflux for 1-2 hours until 4 was completely consumed (monitored by TLC). Then the reaction mixture was cooled down to room temperature. The reaction mixture was passing through a short pad of silica gel to remove K2CO3, and 200 mL acetone was used subsequently to wash the residue. The clear filtration was condensed under vacuum to give a syrup-like residue, which was dissolved in 15 mL HNO3 (68-70% in aqueous as received) at room temperature. The solution was well stirred overnight until the starting material was consumed (monitored by TLC). Compound 5 was precipitated out from the solution (nitration by-products 5a and 5b were still in the solution and were recovered by extraction with CH2Cl2). Simple filtration will afford 5, which was recrystallized from MeOH or EtOAc/Hexane to give large colorless square crystals as pure product in about 50-60% yield. 1H NMR (300 MHz, CDCl3): 7.58 (1H, dd, J = 1.2 Hz, J = 7.2 Hz), 7.47 (1H, tri, J = 8.1 Hz), 7.24 (1H, dd, J = 1.2 Hz, J = 8.1 Hz), 3.90 (3H, s), 3.87 (3H, s). 13C NMR (75 MHz, CDCl3): 163.4, 150.9, 130.8, 123.6, 122.1, 117.1, 56.8, 52.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate | ||
With potassium carbonate | ||
27 g | With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 24h; Cooling with ice; | methyl 3-methoxybenzoate (3): 3-hydroxybenzoic acid (22.7g) was dissolved in DMF (100ml), to this mixture K2CO3 (69g) was added portionwise. Under ice-water bath CH3I (55g) was added dropwise to keep the temperature below 10. The resulting solution was then placed at r.t. to react for 24h. H2O (500ml) AcOEt (500ml) was added, the organic phase was seperated and washed sequentially with brine (300ml), H2O (300ml) and then dried with Na2SO4. The crude product was obtained (light yellow oil, 27g) after filtration and evaporation under reduced pressure. This was used without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sulfuric acid Reflux; | 29.1 Methyl 3-methoxybenzoate A solution of 3-methoxybenzoic acid (20 g, 131.58 mmol, 1.00 equiv) in MeOH (100 mL) and H2SO4 (13 g, 130.00 mmol, 1.00 equiv, 98%) was allowed to react, with stirring in a 250-mL round-bottom flask, overnight under reflux. The reaction was quenched by the addition of 100 mL of water/ice, extracted with 3*100 mL of dichloromethane, and the organic layers combined and dried over anhydrous sodium sulfate. The solids were filtered out. The resulting mixture was concentrated under vacuum yielding 21 g (96%) of methyl 3-methoxybenzoate as yellow oil. |
95% | With sulfuric acid for 0.333333h; Reflux; Microwave irradiation; | |
94% | With sulfuric acid at 110℃; for 0.166667h; Microwave irradiation; |
93% | With toluene-4-sulfonic acid; 2,2-dimethoxy-propane at 60℃; for 48h; | |
90% | With cobalt oxide nanoparticles Co/SBA-15 for 12h; Reflux; | 2.2. Esterification reactions General procedure: Esterification reactions in this study were performed using CoNP catalysts. In a typical reaction, 0.005 mmol of CoNP (0.5 mol.%) was added to a mixture of carboxylic acid precursor (1 mmol) and excess MeOH (molar ratio 1:2) under reflux conditions for 12 h. As soon as the reaction was judged complete using thin-layer chromatography (TLC), the catalyst was separated from the mixture through filtration and then washed with portions of 20 mL ethyl acetate. The product was isolated using a liquid-liquid extraction procedure and dried using Na2SO4. |
90.3% | With sulfuric acid for 8h; Reflux; | Synthesis of methyl benzoate A solution of 3-methoxybenzoic (304 mg, 2.0 mmol) in methanol (5 ml) were heated under reflux until the acid was completely dissolved in methanol then few drops of concentrated sulphuric acid was added to the mixture and refluxed for 8 hr. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of sodium bicarbonate was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried and evaporated to get the required ester (300 mg, 90.3%) as yellow liquid; 1H NMR (400 MHz, CDCl3) δ 8.15 (dd, J = 9.0 Hz, 2H, Ar-H), 7.49 (t, J = 9.0 Hz, 1H, Ar-H), 7.37 (t, J = 9.0 Hz, 2H, Ar-H), 3.85 (s, 3H, OCH3 ester), 3.76 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) δ 166.8, 132.8, 130.1, 129.5, 128.2 (Ar-C), 55.2 (OCH3), 51.8 (OCH3 ester). |
90% | With sulfuric acid at 80℃; | 4.1.1. Methyl 3-methoxybenzoate (2) A mixture of 3-methoxybenzoic (1, 4.24 g, 0.002 mol) and methanol(40 mL) were heated under reflux until the benzoic acid was dissolved in methanol then few drops of concentrated sulphuric acid was added to the mixture and refluxed for 8 h. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of sodium bicarbonate was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried and evaporated to get the required ester compound 2.Yield: 90%. m.p.: 110 C. 1H NMR (400 MHz, CDCl3) δ 7.61 (m, 1H,Ar-H), 7.54 (m, 1H, Ar-H), 7.31 (t, J = 8 Hz, 1H, Ar-H), 7.07 (m, 1H, ArgH), 3.89 (s, 1H, OOCH3), 3.81 (s, 1H, OCH3). 13C NMR (100 MHz,CDCl3) δ 166.85 (Ar-C), 159.86 (Ar-C), 131.41 (Ar-C), 129.6 (Ar-C),122.16 (Ar-C), 119.36 (Ar-C), 114.22 (Ar-C), 55.29 (OOCH3), 52.04(OCH3). |
90% | With sulfuric acid at 80℃; for 8h; | 5.1.1 Methyl 3-methoxybenzoate (2) A mixture of 3-methoxybenzoic (1, 4.24g, 0.002mol) and methanol (40mL) were heated under reflux until the benzoic acid was dissolved in methanol then few drops of concentrated sulphuric acid was added to the mixture and refluxed for 8h. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of sodium bicarbonate was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried and evaporated to get the required ester compound 2. (0046) Yield: 90%. m.p.: 110-112°C. 1H NMR (400MHz, CDCl3) δ 7.61 (m, 1H, Ar-H), 7.54 (m, 1H, Ar-H), 7.31 (t, J=8Hz, 1H, Ar-H), 7.07 (m, 1H, Ar-H), 3.89 (s, 1H, OOCH3), 3.81 (s, 1H, OCH3). 13C NMR (100MHz, CDCl3) δ 166.85 (Ar-C), 159.86 (Ar-C), 131.41 (Ar-C), 129.6 (Ar-C), 122.16 (Ar-C), 119.36 (Ar-C), 114.22 (Ar-C), 55.29 (OOCH3), 52.04 (OCH3). |
90% | With sulfuric acid for 8h; Reflux; | 2.1.1. Synthesis of methyl 3-methoxybenzoate (2) A mixture of 3-methoxybenzoic (1, 5 g, 0.03 mol) and methanol (50mL) were heated under reflux until compound 1 was dissolved in methanol then few drops of concentrated sulfuric acid was added to the mixture and refluxed for 8 h. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of NaHCO3 was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried over anhydrous Na2SO4 and evaporated under vacuum to get the ester derivative 2.Yield: 90%; m.p.: 110-111°C; 1H NMR (400 MHz, CDCl3) δ 7.61 (m,1H), 7.54 (m, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.07 (m, 1H) [Ar-H], 3.89 (s,1H, OOCH3), 3.81 (s, 1H, OCH3); 13C NMR (100 MHz, CDCl3) δ 166.9,159.9, 131.4, 129.6, 122.2, 119.4, 114.2 [Ar-C], 55.3 (OOCH3), 52.0(OCH3). |
90% | With sulfuric acid for 8h; Reflux; | 2.1.1. Synthesis of methyl 3-methoxybenzoate (2) A mixture of 3-methoxybenzoic (1, 5 g, 0.03 mol) and methanol (50mL) were heated under reflux until compound 1 was dissolved in methanol then few drops of concentrated sulfuric acid was added to the mixture and refluxed for 8 h. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of NaHCO3 was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried over anhydrous Na2SO4 and evaporated under vacuum to get the ester derivative 2.Yield: 90%; m.p.: 110-111°C; 1H NMR (400 MHz, CDCl3) δ 7.61 (m,1H), 7.54 (m, 1H), 7.31 (t, J = 8.0 Hz, 1H), 7.07 (m, 1H) [Ar-H], 3.89 (s,1H, OOCH3), 3.81 (s, 1H, OCH3); 13C NMR (100 MHz, CDCl3) δ 166.9,159.9, 131.4, 129.6, 122.2, 119.4, 114.2 [Ar-C], 55.3 (OOCH3), 52.0(OCH3). |
88% | With Oxone In toluene at 60℃; for 48h; Green chemistry; | |
78% | With 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione at 70℃; for 20h; | 3.2.1. General Procedure for the Esterification between Carboxylic Acids and Alcohols General procedure: The mixture of carboxylic acid, alcohol, and 1,3-dibromo-5,5-dimethylhydantoin was stirredin a 25 mL reactor tube at 70 °C for 2-40 h. After reaction completion, the mixture was cooled toroom temperature and the alcohol was evaporated under reduced pressure. The isolation procedurewas as follows, except where noted dierently in the Supporting Information. The residue wasdissolved in 10 mL ethyl acetate and washed with a mixture of 1 mL saturated NaHCO3(aq), 1 mLsaturated Na2S2O3(aq), and 10 mL distilled water, and the water phase was extracted with ethyl acetate(2 10 mL). The organic layers were combined, dried over Na2SO4, and the solvent was evaporatedunder reduced pressure |
58% | With 2-(dimethoxymethylidene)propanedinitrile at 60℃; for 48h; | |
45% | With N-Bromosuccinimide at 70℃; for 20h; | 3.2.1. General Procedure for the Esterification between Carboxylic Acids and Alcohols General procedure: The mixture of carboxylic acid, alcohol and N-bromosuccinimide was stirred in a 25 mL reactortube at 70 °C for 2-40 h. After the completion of the reaction, the mixture was cooled to roomtemperature and alcohol was evaporated under reduced pressure. The isolation procedure was as follows, except where noted differently in Section 3.2.6. The residue was dissolved in ethyl acetate andconsecutively washed with 10 mL of 10% Na2S2O3 (aq), 5 mL of saturated NaHCO3 (aq) and 10 mL ofdistilled water. The water phase was extracted with ethyl acetate (3Χ5 mL). The organic layers were combined, dried over Na2SO4 and the solvent was evaporated under reduced pressure. |
36% | With ammonium cerium(IV) nitrate at 20℃; for 48h; | |
With hydrogenchloride | ||
With sulfuric acid Heating; | ||
With hydrogenchloride at 20℃; | ||
With sulfuric acid at 20℃; for 12h; | ||
With sulfuric acid Heating; | ||
With sulfuric acid Reflux; | ||
With thionyl chloride at 20℃; | General procedure for the synthesis of the hydrazide ligands General procedure: Different substituted carboxylic acids (20 mmol) (A) were stirred with thionyl chloride (100 mmol) in dry methanol (75 ml) or 5-6 h to synthesize corresponding methyl esters (B) (Scheme1). After extraction of esters in chloroform, solvent was evaporated and esters (66 mmol) were refluxed with hydrazine hydrate(330 mmol) in ethanol (75 ml) for 4-5 h. A solid was obtained upon removal of the solvent by rotary evaporation. The resulting solid was washed with hexane to afford hydrazide ligand (C). The spectral and analytical data are given below. | |
With sulfuric acid | ||
With sulfuric acid for 4h; Reflux; | ||
With sulfuric acid for 8h; Reflux; | 4.2 4.2 Methyl 3-methoxybenzoate (5) A mixture of 3-methoxybenzoic (4, 2.12 g, 0.001 mol) and methanol (20 mL) were heated under reflux until the benzoic acid was dissolved in methanol then few drops of concentrated sulfuric acid was added to the mixture and refluxed for 8 h. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of sodium bicarbonate was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried and evaporated to get the required ester compound 5. | |
With thionyl chloride at 20℃; | ||
With sulfuric acid | ||
With sulfuric acid at 65 - 67℃; for 4h; | ||
With sulfuric acid for 8h; Reflux; | ||
With sulfuric acid Reflux; | General procedure for synthesis of hydrazides (5a-l)1 General procedure: Carboxylic acids (10 mmol) were refluxed for 1-2 h in methanol (5 mL) in presence of conc. H2SO4 (catalytic amount) with continuous stirring. The reaction was monitored by TLC till the acids were fully converted to the corresponding esters [Eluent: EtOAc/Hexanes (1:4)]. The reaction mixture was allowed to cool down to room temperature and hydrazine monohydrate 80% (40 mmol, 1.91 mL) was added slowly in an ice bath. The reaction was then warmed to room temperature and refluxed for another 1-2 h and followed by TLC till formation of hydrazide. The reaction mixture was kept at refrigerator till the product precipitated. All hydrazides were isolated in quantitative yields and in a pure form. There melting points were in full agreement with the literature melting points of the same compounds. | |
With sulfuric acid at 85℃; | ||
With sulfuric acid for 8h; Reflux; | Methyl 3-methoxybenzoate (5) A mixture of 3-methoxybenzoic (4, 2.12 g, 0.001 mol) and methanol (20 ml) were heated under reflux until the benzoic acid was dissolved in methanol then few drops of concentrated sulphuric acid was added to the mixture and refluxed for 8 hr. The resulting mixture was cooled to room temperature, diluted with water and a saturated solution of sodium bicarbonate was added to the mixture to neutralize the benzoic acid, extracted with ethyl acetate, dried and evaporated to get the required ester compound 5. | |
With sulfuric acid Reflux; | ||
With sulfuric acid for 8h; Reflux; | 4.2 General procedure for the synthesis of compounds 2a-2q General procedure: The substituted benzoic acid 11q (1 eq.) in methanol was refluxed for 8h. The reactions were completed monitored by TLC (PE/EA=3:1). Then cooling to rt, the solution was adjusted to pH=7 with NaOH. The mixture was extracted with ethyl acetate and washed with brine to give the crude product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | Stage #1: methyl 3-methoxybenzoate With diethylzinc; lithium chloride In tetrahydrofuran; hexane at 20℃; for 6h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; hexane; water at 20℃; for 8h; Inert atmosphere; chemoselective reaction; | |
91% | With HN(CH2CH2C3H3N2Mes)2Cl2; potassium <i>tert</i>-butylate; hydrogen; cobalt(II) chloride In tetrahydrofuran at 100℃; for 16h; Autoclave; Glovebox; | |
90% | With methanol; sodium tetrahydroborate In tetrahydrofuran at 65℃; for 4h; |
65% | With sodium tetrahydroborate In 1,4-dioxane; water for 24h; Ambient temperature; | |
100 % Chromat. | With sodium tetrahydroborate In methanol; 1,2-dimethoxyethane for 1h; Heating; | |
With diisobutylaluminium hydride In diethyl ether; toluene at -70 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium hydroxide In ethanol; water at 20℃; for 6h; | 3-methoxybenzoic acid (4): 3-methoxybenzoic acid (4): 4N NaOH (60ml) was added to a mixture of 3 (12g) in ethanol (60ml). The reaction then proceeds at rt for 6h. Ethanol was evaporated, then 2N HCl was added to adjust the pH to 2~3. The white solids were filtered and dried. m=8.8g. mp 102-104 (reference 105-106). |
91% | With potassium hydroxide In tetrahydrofuran; methanol; water for 5h; Reflux; | |
87% | With sodium hydroxide In methanol; water at 20℃; for 3h; | 3.2 2) Synthesis of 3-methoxybenzoic acid: At room temperature, methyl 3-methoxybenzoate (3.43g, 20.66mmol) was dissolved in a mixed solvent of methanol (5ml): water (10ml) = 1:2, and sodium hydroxide (1.65g, 41.32mmol), react at room temperature for 3h, and monitor the end of the reaction by TLC. After the reaction was completed, the solvent was removed by a rotary evaporator, and dichloromethane (DCM) (30ml) was added, washed with a 5% aqueous hydrochloric acid solution (2×5ml), and the aqueous phase was extracted with dichloromethane (2×5ml) , Combine the organic phases and dry with anhydrous sodium sulfate. The solvent was evaporated to dryness with a rotary evaporator to obtain 2.7 g of white solid 3-methoxybenzoic acid with a yield of 87%. |
86% | With pyridine; iodine; aluminium In acetonitrile at 80℃; for 18h; chemoselective reaction; | m-Anisic acid (16 ). To a suspension of AlI3 (5.5 mmol, 1.0 eq.) in acetonitrile (40 mL) was added pyridine (1.739 g, 22 mmol, 4 eq.) and methyl m-anisate (14, 0.914 g, 5.5 mmol) in sequence. After stirring for 18 h at 80 oC, the mixture was acidified with dilute HCl (2 M, 10 mL), extracted with EA (50 mL 3). The combined organic phases were combined, washed with Na2S2O3, and dried over MgSO4. After filtration, the organic solvents were removed by a rotary evaporator, and the residue was purified through column chromatography (eluent: PE/EA 3:2) to afford 16 (0.723 g, 86%) as a white solid, mp 105.5-106 oC (lit.6 104-105 oC). Rf = 0.68 (PE/EA 1:1). 1H NMR (400 MHz, DMSO-d6) δ S4 13.06 (brs, 1H), 7.54 (d, J = 8 Hz, 1H), 7.45 (t, J = 2.4, 1H), 7.41 (t, J = 8 Hz, 1H), 7.18 (dd, J1 = 8, J2 = 2.4 Hz, 1H), 3.80 (s, 3 H). 13C NMR (100 MHz, DMSO-d6) δ 167.63, 159.65, 132.64, 130.14, 122.00, 119.32, 114.32, 55.65. |
With potassium hydroxide In methanol; water for 4h; Heating; | ||
With potassium hydroxide | ||
With lithium hydroxide In methanol; water at 20℃; for 20h; | ||
With lithium hydroxide In tetrahydrofuran; methanol; water at 20℃; | General synthetic procedure for intermediates 13a-o. General procedure: Step 2: The respective ester was dissolved in THF: CH3OH: H2O (3:3:1), and aqueous LiOH solution (1.0 equiv) was added slowly. The mixture was then stirred at room temperature for 2 h. The solvent was evaporated in vacuum, the product was precipitated by addition of 2 M HCl until a pH of ≤ 2 was reached, filtered off, and dried in vacuum to get intermediates 13a-o. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With ammonia; lithium; <i>tert</i>-butyl alcohol In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With potassium cyanide; oxygen at 60℃; for 3h; chemoselective reaction; | |
92% | With 2,2':6,2''-terpyridine; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; sodium acetate; sodium hydroxide at 90℃; for 12h; Green chemistry; chemoselective reaction; | |
91% | With manganese(IV) oxide; sodium cyanide for 14h; Ambient temperature; |
82% | With potassium carbonate In water at 20℃; for 2h; | (20) General Procedure for the Oxidation General procedure: A mixture of bromine chloride resin and K2CO3 in MeOH-H2O (8:2) 3 mL was placed in a round-bottom flask fitted with amagnetic stirrer. To this, the aldehyde (1 mmol, 1 equiv) was added dropwise, and the reaction mixture stirred at r.t. The progress of the reaction was monitored by TLC. After completionof the reaction the mixture was filtered, and the filtrate was extracted with Et2O. The ether layer was washed with H2O, brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography, if required, over silicagel (60-120 mesh) using a mixture of PE and EtOAc (9:1) as eluent. |
79% | With iodine; potassium hydroxide at 0℃; for 4h; | |
77% | With 4-ethyl-1-methyl-4H-[1,2,4]-triazol-1-ium iodide; 1,8-diazabicyclo[5.4.0]undec-7-ene In tetrahydrofuran at 45℃; for 68h; | |
75% | With tert.-butylhydroperoxide; potassium carbonate In water at 60℃; for 6h; | |
68% | With dihydrogen peroxide In methanol for 68h; Ambient temperature; | |
54% | With 1-(ferrocenylbutyl)-4-(3-methylimidazolium) tetrafluoroborate; iodine; potassium carbonate at 50 - 60℃; for 22h; Inert atmosphere; | Oxidative esterification of aryl aldehydes General procedure: In a 25 ml one-necked, round bottomed flask aryl aldehyde (2.5 mmol), ionic liquids (7.5 mmol), reagents (2.0 mmol), and alcohol (7.5 mmol) were mixed thoroughly and stirred at 50-60 °C. The completion of the reaction was monitored by TLC using (EtOAc/hexane 1:9) as eluent and the product was isolated through preparative chromatography from EtOAc/hexane as eluent. |
46% | With water; iodine; sodium nitrite at 70℃; for 0.2h; Microwave irradiation; chemoselective reaction; | |
With iodine; potassium hydroxide at 0℃; for 2h; | ||
With oxygen; potassium carbonate at 80℃; for 12h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With ammonia; lithium; <i>tert</i>-butyl alcohol In tetrahydrofuran |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | With sodium methylate In diethyl ether at 25 - 35℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With nitric acid; In water; at 20℃; | Synthesis of 5. 3-Hydroxybenzoic acid (Acros) (1.38 g) was dissolved in acetone (40 mL), then K2CO3 (3.0 g) and dimethyl sulfate (2.7 g) were added in one portion. The mixture was heated to reflux under stirring for 1-2 hours until 3-hydroxybenzoic acid was completely consumed to form 4 (monitored by TLC). Then the reaction mixture was cooled down to room temperature, and filtered through a short pad of silica gel to remove K2CO3. The resulting solid residue was washed with acetone (200 mL). The clear filtration was concentrated under vacuum to give a syrup-like residue, which was dissolved in 15 mL HNO3 (68-70% in aqueous as received) at room temperature. The solution was well stirred overnight until the starting material was consumed (monitored by TLC). Compound 5 was precipitated out from the solution (nitration by-products 5a and 5b were still in the solution and were recovered by extraction with CH2Cl2). Simple filtration will afford 5, which was recrystallized from MeOH or EtOAc/Hexane to give large colorless square crystals as pure product in about 50-60% yield. 1H NMR (300 MHz, CDCl3): 7.58 (1H, dd, J=1.2 Hz, J=7.2 Hz), 7.47 (1H, tri, J=8.1 Hz), 7.24 (1H, dd, J=1.2 Hz, J=8.1 Hz), 3.90 (3H, s), 3.87 (3H, s). 13C NMR (75 MHz, CDCl3): 163.4, 150.9, 130.8, 123.6, 122.1, 117.1, 56.8, 52.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 8% 2: 80% | With tert-Amyl alcohol; sodium hydride In tetrahydrofuran at 40℃; for 17h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 80% 2: 8% | With methanol; tert-Amyl alcohol; sodium hydride In tetrahydrofuran at 40℃; for 17h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With oxygen In chloroform-d1 at 0℃; for 0.5h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With oxygen In chloroform-d1 at 0℃; for 0.5h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With oxygen In chloroform-d1 at 0℃; for 0.5h; Irradiation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With N,N,N,N,-tetramethylethylenediamine; lithium diisopropyl amide In tetrahydrofuran; hexane at -78 - 20℃; | |
Stage #1: ethyl acetoacetate With N,N,N,N,-tetramethylethylenediamine; lithium diisopropyl amide Stage #2: methyl 3-methoxybenzoate Stage #3: With acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With sodium hydride In N,N-dimethyl-formamide at 20℃; for 16h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: methyl 3-hydroxybenzoate With sodium hydride In N,N-dimethyl-formamide at 0℃; for 0.333333h; Stage #2: methyl iodide In N,N-dimethyl-formamide at 20℃; for 15h; | |
63% | With sodium hydride In N,N-dimethyl-formamide; mineral oil at 20℃; for 22.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With C57H43IP2Pd; triethylamine at 90℃; for 12h; Autoclave; | |
96% | With triethylamine at 130℃; for 2h; | |
63% | With palladium diacetate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide; toluene at 100℃; continuous flow reactor; |
63% | With palladium diacetate; triethylamine; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In N,N-dimethyl-formamide; toluene at 100℃; Flow reactor; | |
86 % Chromat. | With triethylamine at 105℃; for 19h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With ammonium acetate; magnesium In methanol at 20℃; for 2.5h; | |
92% | With ammonium acetate; methanol; magnesium at 20℃; for 2.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.833333h; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran for 2.5h; | 1a.1 LDA (44.2 ml. of a 2M solution in THF, 88.5 mmol) was added dropwise over 20 minutes to a cold (-78 0C) solution of acetonitrile (2.8 ml_, 53.6 mmol) in THF (63 mL) under an atmosphere of nitrogen. The reaction mixture was stirred for 30 minutes and a solution of methyl 3-methoxybenzoate (7.00 g, 42.1 mmol) in THF (63 mL) was added dropwise over 30 minutes. The reaction mixture was stirred for 2 hours, quenched with a saturated aqueous solution of ammonium chloride (100 mL), allowed to warm to room temperature and diluted with Et2O (300 mL). The aqueous layer was separated and extracted with Et2O (100 mL). The combined organic layers were washed with 1 M HCI (200 mL), brine, dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (25-30 % EtOAc in heptane) to afford the title compound as a pale orange solid (6.16 g, 83 % yield). 1H NMR (300 MHz, CDCI3) 7.50-7.42 (3H, m), 7.24-7.20 (1 H, m), 4.10 (2H, s), 3.89 (3H, s). |
70% | With lithium diisopropyl amide In tetrahydrofuran; hexane at -50℃; for 3h; Inert atmosphere; | |
64% | Stage #1: methyl 3-methoxybenzoate; acetonitrile With sodium hydride In toluene at 90℃; Stage #2: In water Aqueous acetate buffer; | 27A Example 27A; 3- (3-Methoxyphenyl)-3-oxopropanenitrile; 32.6 g (815 mmol) of sodium hydride (60% suspension in mineral oil), 43 ml (815 mmol) acetonitrile and 73.4 g (407 mmol) methyl 3-methoxybenzoate are stirred at 90°C in 540 ml toluene overnight. The precipitate is collected by suction and washed with toluene. The combined organic phases are extracted with water. The aqueous phase is combined with the solid residue, acidified to pH 5 and then extracted three times with DCM. The combined DCM phases are washed with brine, dried over sodium sulfate and the solvent is removed in vacuum. The residue is treated with diethyl ether, and the crystals are collected by suction and washed with diethyl ether to yield 46.9 g (64% of th.) of the title compound. 'H-NMR (200 MHz, CDC13) : 8 = 3. 83 (s, 3H), 4.77 (s, 2H), 7.23-7. 55 (m, 4H). |
Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran | ||
Stage #1: acetonitrile With lithium diisopropyl amide In tetrahydrofuran at -78℃; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at -78 - 20℃; | ||
With sodium ethanolate at 80℃; | ||
Stage #1: acetonitrile With n-butyllithium In hexane; toluene at -78℃; for 0.333333h; Inert atmosphere; Stage #2: methyl 3-methoxybenzoate In hexane; toluene at 20℃; for 0.333333h; Inert atmosphere; | ||
29 g | With potassium <i>tert</i>-butylate In tetrahydrofuran | 49.a a) Synthesis of 3-(3-Methoxy-phenyl)-3-oxo-propionitrile 42 g of 2-methoxybenzoic acid methyl ester and 10.4 g of acetonitril were dissolved in 300 ml of THF, and 28 g of potassium tert.-butylate were added with vigorous stirring. The mixture warmed up, and stirring was continued as good as possible. A precipitate was formed, that was filtered off after 3 h and washed with diethyl ether. After drying, the solid was dissolved in ca. 200 ml of water, and the pH was adjusted to 5-6 with formic acid. The precipitate was collected, washed with water and dried to yield 29 g. |
With sodium hydride In toluene; mineral oil for 24h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Ki; sulfuric acid; sodium nitrite; In ethanol; water; | A stirred solution of methyl 4-amino-3-methoxybenzoate (725 mg, 4 mmol) in EtOH (10 mL) was added to dil.H2SO4 (prepared from H2SO4 0.5 mL and H2O 10 mL) at 0 C. A solution of NaNO2 (331 mg, 4.8 mmol) in H2O (10 mL) was added to the mixture. After stirring for 0.5 hr at the same temp, the mixture was poured into a cooled (0 C.), stirred suspended solution of KI (1.83 g, 11 mmol) and cat. Cu in H2O (100 mL). The mixture was vigorously stirred for 1 hr at room temp and extracted with CHCl3. The extract was washed with brine, dried over MgSO4, and evaporated. The residue was chromatographed on silica-gel with n-hexane-EtOAc (10:1, v/v) as eluent to give a mixture of methyl 4-iodo-3-methoxybenzoate and methyl 3-methoxybenzoate (748 mg) as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
12.24 g (72.7%) | With n-butyllithium; sodium chloride In tetrahydrofuran | R.12 Reference Example 12 STR93 In an atmosphere of argon, 13.0 ml (92.8 mmol) of diisopropylamine was added to 75 ml of anhydrous THF, and the solution was stirred at room temperature. To this solution, 55.0 ml (89.1 mmol) of butyl lithium (1.62M hexane solution) was added, and the mixture was stirred for 30 minutes. This solution was then cooled to -78° C., and 15.0 ml (89.5 mmol) of ethyl t-butylacetate was added, and the mixture was stirred for 20 minutes. To this mixture, 10.05 g (60.5 mmol) of methyl 3-methoxybenzoate (Compound [12]) was added, and the solution was stirred at -78° C. for 2 hours and 40 minutes, and then at 0° C. for 1 hour and 30 minutes. This reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The extracted layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was chromatographed on silica gel and eluted with dichloromethane, whereby ethyl 2-t-butyl-2-(3-methoxybenzoyl)acetate (Compound [77]) was obtained in the form of a colorless oil in a yield of 12.24 g (72.7%). 1 H-NMR (300 MHz, CDCl3): δ 1.15 (s, 9H), 1.18 (t, J=7.2 Hz, 3H), 3.86 (s, 3H), 4.13 (q, J=7.2 Hz, 2H), 4.28 (s, 1H), 7.11 (d with fine coupling, J=8.3 Hz, 1H), 7.37 (dd, J=8.3 and 7.6 Hz, 1H), 7.48 (s with fine coupling, 1H), 7.54 (d, J=7.6 Hz, 1H) ppm. IR (liquid film): 2964, 2912, 1736, 1696, 1598, 1582 cm-1. Mass (m/z, %): 278 (M+, 10), 222 (26), 176 (18), 135 (100). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
454 mg (46.7%) | With sodium chloride; sodium hydrogencarbonate; triethylamine In tetrahydrofuran; hexane; dichloromethane; water | 39 EXAMPLE 39 STR72 EXAMPLE 39 STR72 In an atmosphere of argon, 5 g (32 mmol) of titanium trichloride was suspended in 100 ml of anhydrous THF. This mixture was stirred for 25 minutes and then ice-cooled. To this ice-cooled suspension, 608 mg (16 mmol) of lithium aluminum hydride was added, and the solution was stirred for 30 minutes. To this reaction solution, with the temperature thereof raised to room temperature, 2.3 ml (16 mmol) of triethylamine was added, and the solution was refluxed for 30 minutes. To the thus refluxed solution, a solution of 531 mg (3.2 mmol) of methyl 3methoxybenzoate (Compound [12]) and 1.026 g (6.04 mmol) of 2,2,6,6-tetramethylheptan-3-one in 20 ml of anhydrous THF was added dropwise. This reaction solution was further refluxed for 75 minutes. This reaction solution was then ice-cooled and water was added dropwise thereto. The reaction mixture was then extracted with ethyl acetate. The extracted layer was successively washed with water, a saturated aqueous solution of sodium hydrogencarbonate and a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate and concentrated. The residue was chromatographed on silica gel and eluted with a mixed solvent of hexane and dichloromethane (6:1), whereby 2-t-butyl-1-methoxy-1-(3-methoxyphenyl)-5,5-dimethyl-1-hexene (Compound [55]) was obtained in the form of a colorless oil in a yield of 454 mg (46.7%). 1 H-NMR (300 MHz, CDCl3): δ 0.62 (s, 9H), 1.15 (dt, J=8.7 and 4.4 Hz, 2H), 1.25 (s, 9H), 1.81 (dt, J=8.7 and 4.4 Hz, 2), 3.17 (s, 3H), 3.81 (s, 3H), 6.78-6.86 (m, 3H), 7.24 (t, J=7.8 Hz, 1H) ppm. IR (liquid film): 2956, 1598, 1578, 1484, 1298, 1222, 1130 cm-1. Mass (m/z, %): 304 (M+, 73), 289 (100), 233 (85), 219 (39), 201 (22), 177 (32). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With silica-SMAP-Ir(OCH3)(C8H12) In hexane ligand reacted with B-compound in hexane in presence of Ir-complex as catalyst at 40°C for 1 h; | |
78% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; diisopropyl(2-(isopropylthio)phenyl)silane In 2-methyltetrahydrofuran at 60℃; for 22h; Inert atmosphere; | 8 Application example 8 This example is a milligram level preparation of methyl 2-formate-4-methoxy-phenylboronic acid pinacol ester, which specifically includes the following steps:Under argon atmosphere, add methyl 3-methoxybenzoate (83mg, 0.5mmoL) bis(pinacolato)diboron (254mg, 1mmoL) to the reaction vessel,1,5-cyclooctadiene methoxyiridium dimer (5mg, 0.0075mmol, 1.5%),Thiosilane ligand (4.50mg, 0.015mmol, 3%, formula L2) and 2-methyltetrahydrofuran (0.5mL), react at 60°C for 22h,After the reaction, the solvent (2-methyltetrahydrofuran) was removed by rotary evaporation (40-50°C), and column chromatography was used (using 300 mesh silica gel,The mass ratio of silica gel to the material to be purified is 100:1, the eluent is petroleum ether and ethyl acetate, and the volume ratio is 20:1) to purify the product,A yellow methyl 2-formate-4-methoxy-phenylboronic acid pinacol ester (113.9 mg, 78%, formula (12)) was obtained,The NMR spectrum of the product is exactly the same as the reported NMR information. |
50% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; diisopropyl(2-(isopropylthio)phenyl)silane In 2-methyltetrahydrofuran at 80℃; for 16h; Sealed tube; Inert atmosphere; Glovebox; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With Silica-SMAP-Ir(OMe)(cod) In hexane at 40℃; for 1h; Autoclave; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With sulfuric acid In acetic acid at 20℃; for 50h; | 33.A To a mixture of 3- methoxymethyl-benzoate (0.45 g, 2.7 mmol) and 1 -adamantanol (0.41 g, 2.7 mmol) in AcOH (3 ml) was added concentrated H2SO4 (0.5 mL) and the reaction mixture was stirred for 50 h at room temperature. The crude mixture was taken in EtOAc (100 ml) and washed with NaHCO3 solution, dried over MgSO4 and filtered. The filtrate was evaporated to dryness and the residue was crystallized from MeOH to give the title compound (0.81 g, 95%), as a colourless solid. 1 H- NMR, (CDCI3) 1 .76 (s, 6H); 2.07 (bs, 9H); 3.87 (s, 3H); 3.88 (s, 3H); 7.25 (d, 1 H); 7.49 (d, 1 H, J = 1.63 Hz); 7.57 (dd, 1 H, J = 8.1 , 1.7 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | Stage #1: picoline With sodium hexamethyldisilazane In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at 0℃; for 1h; | 8.A.e To a solution of 4-methyl-pyridine (1.04 mL, 10.74 mmol) in anhydrous tetrahydrofuran (40 mL) at 00C a 1 M solution of sodium hexamethyldisilazide in tetrahydrofuran (21.5 mL, 21.5 mmol, 2 eq) was added dropwise and the reaction was stirred for 20 minutes. Neat methyl 3-methoxybenzoate (1.8 g, 10.74 mmol, 1 eq) was then added and the reaction was stirred at 00C for one hour. The reaction was poured into saturated ammonium chloride solution and, after basification with saturated aqueous NaHCU3, extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was taken up with n-hexane and filtered to give 1.75 g (72%) of the desired product as beige solid (1.775 g, 50%).HPLC (254 nm): R1: 5.13 min.1H NMR (401 MHz, DMSOd6) δ = 8.52 (d, J = 5.9 Hz, 2 H), 7.66 (ddd, J = 0.9, 1.6, 7.7 Hz, 1 H), 7.53 (dd, J = 1.6,2.4 Hz, 1 H), 7.49 (t, J = 7.9 Hz, 1 H), 7.30 (d, J = 6.0 Hz, 2 H), 7.25 (ddd, J = 0.9, 2.7, 8.2 Hz, 1 H), 4.49 (s, 2 H),3.84 (s, 3 H). HRMS (ESI) calcd for C14H14NO2 [M+H]+ 228.1019, found 228.1017. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With bis(1,5-cyclooctadiene)nickel(0); (dimethoxy)methylsilane; tricyclohexylphosphine In toluene at 80℃; for 12h; Inert atmosphere; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With bis-triphenylphosphine-palladium(II) chloride; potassium carbonate; benzyl chloride In tetrahydrofuran at 65 - 70℃; for 20h; Inert atmosphere; Schlenk technique; | |
94% | With oxygen at 70℃; for 16h; | |
93% | With oxygen; potassium carbonate at 60℃; for 20h; |
92% | With bismuth(III) chloride; palladium diacetate; potassium carbonate at 20℃; for 2h; chemoselective reaction; | |
91.5% | With potassium carbonate at 60℃; for 2h; | |
88% | Stage #1: methanol With sodium tetrachloroaurate(III) dihyrate; potassium carbonate at 20℃; for 0.0166667h; Green chemistry; Stage #2: 3-methoxybenzyl alcohol at 20℃; for 0.0333333h; Green chemistry; Stage #3: With oxygen at 80℃; Autoclave; Green chemistry; | |
87% | With Au#Co; oxygen; potassium carbonate at 80℃; for 7h; Autoclave; | 7 Example 7: Synthesis of Methyl Methoxybenzoate 20 mg of Au-Co composite particle support (0.1 mol%), 13.8 mg of K2CO3 (10 mol%), 138 mg of m-methoxybenzyl alcohol (1 mmol),4 mL of methanol was sequentially added to an autoclave with a 25 mL glass lining.After replacing the oxygen three times, the pressure is increased to 0.1 MPa, and the reaction at 80 ° C for 7 hours.Cool to room temperature and slowly deflate and depressurize.Filter the catalyst,The filtrate was concentrated by rotary evaporation and the residue was subjected to chromatography.Obtaining 144.4 mg of methyl methoxybenzoate as a colorless liquid product.The yield was 87%. |
86% | With dichloro bis(acetonitrile) palladium(II); silver tetrafluoroborate; oxygen; sodium t-butanolate at 45℃; Cooling with ice; | |
83% | With 1H-imidazole; tert.-butylhydroperoxide; tetra-(n-butyl)ammonium iodide In water at 80℃; for 9h; Green chemistry; chemoselective reaction; | General procedure: To a mixture of benzyl alcohol (108 mg, 1.0 mmol) and TBHP(180 mg, 2.0 mmol) in water (3 ml), the catalyst TBAI (73.8 mg,0.2 mmol), imidazole (136 mg, 2.0 mmol), and MeOH (2 ml)were added, and the mixture was stirred at 80 °C for 8 h. Theprogress of the reaction was monitored by TLC. After completionof reaction, the reaction mixture was cooled to room temperature.Then MeOH was distilled out, and the organic productwas extracted with ethyl acetate (3 × 10 ml), repeatedly washedwith distilled water (4 × 5 ml) to remove the unreacted TBHP,dried with anhydrous sodium sulfate, and the solvent was evaporatedunder reduced pressure to afford methyl benzoate (112mg, yield 82%). |
83% | With C25H19BrMnN2O2P; potassium <i>tert</i>-butylate In toluene at 120℃; for 24h; | |
81% | With [ruthenium(II)(η6-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]2; (2-((2-(diphenylphosphanyl)ethyl)(quinolin-2-ylmethyl)amino)ethyl)diphenylphosphine oxide; potassium carbonate In n-heptane at 120℃; for 16h; | |
73% | With trichloro(2,2':6',2''-terpyridine)rhodium(III); sodium hydrogencarbonate at 90℃; for 18h; Green chemistry; chemoselective reaction; | |
92 %Chromat. | With oxygen; potassium carbonate at 60℃; for 24h; Schlenk technique; Green chemistry; | |
With oxygen at 79.84℃; for 6h; Autoclave; | Catalytic reaction General procedure: The oxidative esterification of MAL and other aldehydes or alcohols to methyl esters was performed in a batch-type Teflon-lined stainless-steel autoclave. Typically, MAL purchased from Alfa Aesar (12 mmol) and the catalyst (typically, 0.50 g) were added into the reactor pre-charged with methanol (20 mL). After the introduction of O2 with a certain pressure (typically 0.2 MPa), the mixture was heated up to a reaction temperature (typically 343 K) in an oil bath, and then the catalytic reaction was started by vigorously stirring. After a fixed time (typically 2 h, recorded as reaction time), the reaction was stopped by cooling down the reactor to room temperature in cold water. The products were analyzed by a gas chromatograph equipped with a FID detector and a capillary column (DB-FFAP, 60 m × 0.32 mm × 0.25 μm) using ethanol as an external standard for quantification. | |
96 %Chromat. | With oxygen; potassium carbonate at 70℃; for 5h; Autoclave; | |
With oxygen at 60℃; for 12h; chemoselective reaction; | ||
With oxygen at 60℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With sodium hexamethyldisilazane In tetrahydrofuran; N,N-dimethyl-formamide at -10℃; for 3.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 86% 2: 8% | Stage #1: 3-methoxyphenyl bromide With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Stage #2: N,N-dimethyl-formamide In tetrahydrofuran; hexane at -78 - 20℃; for 2h; Stage #3: methanol Further stages; | 4.3. Typical procedure for one-pot conversion of aromatic bromides into aromatic methyl esters with DMF General procedure: n-BuLi (1.67 M solution in hexane, 1.3 mL, 2.2 mmol) was added dropwise into a solution of p-bromoanisole (383 mg, 2.0 mmol) in THF (3 mL) at -78 °C for 30 min. Then, DMF (0.22 mL, 2.2 mmol) was added to the mixture and the obtained mixture was stirred at rt. After 2 h at the same temperature, THF was removed. Then, MeOH (3 mL) was added to the residue and the mixture was stirred at room temperature. After 30 min, I2 (1523 mg, 6 mmol) and K2CO3 (829 mg, 6 mmol) were added at 0 °C and the obtained mixture was stirred for 22 h at rt. The reaction mixture was quenched with satd aq Na2SO3 (5 mL) and was extracted with CHCl3 (3×20 mL). The organic layer was washed with brine and dried over Na2SO4 to provide methyl 4-methoxy-1-benzoate in 82% yield. If necessary, the product was purified by short column chromatography (SiO2:hexane:EtOAc=9:1) to give pure methyl 4-methoxybenzoate as a colorless oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | Stage #1: methyl 3-methoxybenzoate With naphthalene; lithium In tetrahydrofuran at -78 - 20℃; for 1h; Inert atmosphere; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; | 29.2 2-hydroxy-1,2-bis(3-methoxyphenyl)ethanone To a solution of naphthalene (12.4 g, 96.88 mmol, 3.23 equiv) in THF (100 mL) at -10° C. under an inert atmosphere was added Li (630 mg, 90.00 mmol, 3.00 equiv), and the resulting solution was allowed to react, with stifling, overnight at room temperature. Upon cooling to -78° C. a solution of methyl 3-methoxybenzoate (5 g, 30.12 mmol, 1.00 equiv) in THF (20 mL) was added and allowed to react, with stifling, for an additional 1 hr at room temperature. The reaction was quenched by 6.5 g of Me3SiCl at 0° C. and stirred for 30 min. at room temperature. After further cooling to 0° C., 30 ml of H2O was added dropwise, then extracted by ethyl acetate (100 mL for 3 times). The organic layers were concentrated and purified by column chromatography (petroleum ether:ethyl acetate 10:1) affording 3.5 g (43%) of 2-hydroxy-1,2-bis(3-methoxyphenyl)ethanone as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With Methyl formate; copper(l) chloride In methanol at 110℃; for 2h; Autoclave; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With dimanganese decacarbonyl at 180℃; for 1h; | Methyl 3-methoxybenzoate. General procedure: General procedure for the alkylation of phenols with dimethyl carbonate. A 17-mL stainless steel high-pressure micro reactor was charged with 3 mmol of Mn2(CO)10, W(CO)6, or Co2(CO)8, 100 mmol of the corresponding phenol, and 300 mmol of dimethyl carbonate, and the reactor was hermetically closed and heated for 1 h at 180°C. The reactor was then cooled to room temperature and opened, and the mixture was filtered through a layer of alumina. Unreacted dimethyl carbonate was distilled off, and the residue was distilled under atmospheric or reduced pressure or recrystallized from ethanol. Methyl 3-methoxybenzoate. Yield 99%, bp 96-97°C (3 mm). 13C NMR spectrum, δC, ppm: 52.42 (OCH3), 56.16 (OCH3), 113.93 (C2), 119.15 (C4), 121.86 (C6), 129.19 (C5), 131.70 (C1), 159.42 (C3), 166.42 (C=O). Found, %: C 64.95; H 6.03. C9H10O3. Calculated, %: C 65.05; H 6.07. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With titanium(IV) isopropylate In tetrahydrofuran at 0 - 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69.9% | With lithium hexamethyldisilazane In tetrahydrofuran at -25 - 25℃; | Synthesis of 2-(2-bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one To a solution of methyl benzoate (775 mg, 5.0 mmol) and 2-bromo-4-picoline (0.5 mL, 5.6 mmol) in anhydrous THF (5 mL) in a cooled bath at -25° C, LiHMDS (3.7 mL, 1.0M solution in THF, 19.9 mmol) was slowly added to maintain the temperature at -25 °C. The resulting mixture was stirred overnight at room temperature. The mixture was quenched with saturated aqueous NH4Cl. Ethyl acetate was added and the organic layer was separated. The aqueous layer was extracted with ethyl acetate (3 x10 mL). The combined organic layer extracts were washed with brine and dried over anhydrous Na2SO4. The organic solvent was evaporated under reduced pressure and the residue was purified by flash column chromatography (silica gel, hexane ethyl acetate 12:1 v/v then switching to hexane-ethyl acetate 10:1 v/v) to yield 2-(2-Bromopyridin-4-yl)-1-(3-methoxyphenyl) ethan-1-one (17) (1.0 g, 69.9 %) as light yellow solid; m.p.85-88°C |
45% | With lithium hexamethyldisilazane In tetrahydrofuran at -25 - 20℃; | 4.3 4.3 2-(2-Bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (6) A solution of compound 5 (1.0 g, 5.0 mmol) and 2-bromo-4-picoline (0.5 mL, 5.6 mmol) in THF (5 mL) was cooled to -25 °C, and LiHMDS (3.7 mL,1.0 M solution in THF, 19.9 mmol) was slowly added thereto to maintain the temperature at -25 °C. The resulting mixture was stirred overnight at room temperature. The mixture was quenched with saturated aqueous NH4Cl (15 mL), and ethyl acetate (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 * 10 mL). The combined organic layer was washed with saline and dried over anhydrous sodium sulfate. The organic solvent was evaporated under vacuum and the residue was purified by flash column chromatography (silica gel, hexane ethyl acetate 1:1 v/v then switching to hexane-ethyl acetate 1:5 v/v) to yield the title compound (0.58 g, 45%). mp: 85-88 °C; 1H NMR (400 MHz, CDCl3) δ 8.30 (d, 1H, J = 4.8 Hz), 7.55 (d, 1H, J = 7.6 Hz), 7.56-7.48 (m, 1H), 7.40 (t, 2H, J = 8.0 Hz), 7.15 (m, 2H), 4.25 (s, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.0, 150.0, 146.5, 137.3, 129.9, 129.2, 124.2, 121.0, 120.2, 112.8, 55.5, 44.0. |
45% | With lithium hexamethyldisilazane In tetrahydrofuran | 2-(2-Bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (6) A solution of compound 5 (1.0 g, 5.0 mmol) and 2-bromo-4-picoline (0.5 mL, 5.6 mmol) in THF (5 mL) was cooled to -25 °C, and LiHMDS (3.7 mL,1.0M solution in THF,19.9 mmol) was slowly added thereto to maintain the temperature at -25° C. The resulting mixture was stirred overnight at room temperature. The mixture was quenched with saturated aqueous NH4Cl (15 mL), and ethyl acetate (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 x 10 mL). The combined organic layer was washed with saline and dried over anhydrous sodium sulfate. The organic solvent was evaporated under vacuum and the residue was purified by flash column chromatography (silica gel, hexane ethyl acetate 1:1 v/v then switching to hexane-ethyl acetate 1:5 v/v) to yield the title compound (0.58 g, 45%). |
With lithium hexamethyldisilazane In tetrahydrofuran at -25 - 20℃; | ||
With lithium hexamethyldisilazane In tetrahydrofuran for 18h; | 4.1.2. 2-(2-Bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (4) A solution of compound 2 (1.0 g, 5.0 mmol) and 2-bromo-4-picoline(0.5 mL, 5.6 mmol) in THF (5 mL) was cooled to 25 C, and LiHMDS(3.7 mL, 1.0 M solution in THF, 19.9 mmol) was slowly added at 25°C to the reaction mixture maintaining the temperature at 25°C. The resulting mixture was stirred overnight at room temperature. The mixture was quenched with saturated aqueous NH4Cl (15 mL), and ethylacetate (20 mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3-10 mL). The combined organic layer was washed with saline and dried over anhydroussodium sulphate. The organic solvent was evaporated under vacuumand the residue was purified by flash column chromatography(silica gel, hexane ethyl acetate 1:1 v/v then switching to hexane-ethylacetate 1:5 v/v) to yield the title compound 4, which was subjected tothe next step without further purification. | |
With lithium hexamethyldisilazane In tetrahydrofuran for 18h; | 5.1.2 2-(2-Bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (3) A solution of compound 2 (1.0g, 5.0mmol) and 2-bromo-4-picoline (0.5mL, 5.6mmol) in THF (5mL) was cooled to -25°C, and LiHMDS (3.7mL, 1.0M solution in THF, 19.9mmol) was slowly added at -25°C to the reaction mixture maintaining the temperature at -25°C. The resulting mixture was stirred overnight at room temperature. The mixture was quenched with saturated aqueous NH4Cl (15mL), and ethyl acetate (20mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3-10mL). The combined organic layer was washed with saline and dried over anhydrous sodium sulfate. The organic solvent was evaporated under vacuum and the residue was purified by flash column chromatography (silica gel, hexane ethyl acetate 1:1 v/v then switching to hexane-ethyl acetate 1:5 v/v) to yield the title compound 4, which was subjected to the next step without further purification. | |
Stage #1: 2-Bromo-4-picoline With lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at -70 - 20℃; for 6h; Inert atmosphere; | 2.1.2. Synthesis of 2-(2-bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (3) To a solution of 2-bromo-4-picoline (0.5 mL, 5.6 mmol) in THF (20mL) at -70°C, LiHMDS (11 mL, 1.0 M solution in THF, 10.8 mmol) was slowly added under N2 to the reaction mixture maintaining the temperature at -70°C. After 30 minutes, a solution of compound 2 (1.0 g, 5.0mmol) in THF (10 mL) was slowly added to the reaction mixture under N2 at -70°C. The resulting mixture was stirred for 6 hours at room temperature. The mixture was quenched with saturated aqueous NH4Cl(20 mL), and ethyl acetate (30 mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 -10mL). The combined organic layer was washed with saline and dried over anhydrous Na2SO4, evaporated under vacuum to yield the title compound 3, which were subjected to the next step without further purification. | |
Stage #1: 2-Bromo-4-picoline With lithium hexamethyldisilazane In tetrahydrofuran at -70℃; for 0.5h; Inert atmosphere; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at -70 - 20℃; for 6h; Inert atmosphere; | 2.1.2. Synthesis of 2-(2-bromopyridin-4-yl)-1-(3-methoxyphenyl)ethan-1-one (3) To a solution of 2-bromo-4-picoline (0.5 mL, 5.6 mmol) in THF (20mL) at -70°C, LiHMDS (11 mL, 1.0 M solution in THF, 10.8 mmol) was slowly added under N2 to the reaction mixture maintaining the temperature at -70°C. After 30 minutes, a solution of compound 2 (1.0 g, 5.0mmol) in THF (10 mL) was slowly added to the reaction mixture under N2 at -70°C. The resulting mixture was stirred for 6 hours at room temperature. The mixture was quenched with saturated aqueous NH4Cl(20 mL), and ethyl acetate (30 mL) was added. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (3 -10mL). The combined organic layer was washed with saline and dried over anhydrous Na2SO4, evaporated under vacuum to yield the title compound 3, which were subjected to the next step without further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran at 0 - 20℃; Inert atmosphere; | 5.2.2. Synthesis of methyl alkoxy benzoate (B) General procedure: To a solution of methyl hydroxy benzoate (1 eq) in dry THF wereadded alcohol (1 eq) and triphenylphosphine (PPh3) (1.2 eq). The reactionmixture was allowed to stir at 0 °C (ice bath) for 15 min.Diisopropyl azodicarboxylate (DIAD) (1.2 eq) was added dropwise intothe cold solution and then stirred at room temperature for overnightunder N2. The mixture was diluted with water and extracted with ethylacetate twice, and the combined organic phase was washed with brinesolution, dried with Na2SO4, filtrated, and concentrated under reducedpressure. The residue was purified on a silica gel column. | |
With thionyl chloride at 20℃; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | Stage #1: (S)-methyl p-tolyl sulfoxide With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 0.5h; Inert atmosphere; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran for 2h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | Stage #1: methyl 3-methoxybenzoate With potassium phosphate; 2,2,2-trifluoroethanol In 1,4-dioxane at 125℃; for 0.5h; Sealed tube; Schlenk technique; Inert atmosphere; Stage #2: benzyl-methyl-amine In 1,4-dioxane at 125℃; for 22h; Sealed tube; Schlenk technique; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With copper(I) oxide; di-tert-butyl peroxide In <i>tert</i>-butyl alcohol at 120℃; for 24h; Sealed tube; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine In acetonitrile at 100℃; for 24h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With diiron nonacarbonyl at 180℃; for 1h; Sealed tube; | General procedure for the reaction of dimethyl carbonate with carboxylic acids. General procedure: 1-3 mmol of catalyst Mn 2 (CO) 10 , 100 mmol of the carboxylic acid, and 300-400 mmol of dimethyl carbonate were placed into a 17 mL stainless steel microreactor. The reactor was sealed, and the reaction mixture was heated at 180° for 1 h. After the reaction was complete, the reactor was cooled to room temperature and opened. The reaction mixture was filtered through a layer of Al 2 O 3 . Unreacted dimethyl carbonate was distilled off, the residue was distilled at atmospheric or reduced pressure, or crystallized. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With iodine; aluminium In acetonitrile at 80℃; for 18h; | m-Hydroxybenzoic acid (15). To a suspension of AlI3 (15 mmol, 3.0 eq.) in acetonitrile (200 mL) was added methyl m-anisate (14, 0.833 g, 5 mmol). After stirring for 18 h at 80 oC, the mixture was acidified with dilute HCl (2 M, 20 mL), extracted with EA (100 mL 3). The combined organic phases were combined, washed with Na2S2O3, and dried with MgSO4. After filtration, the organic solvents were removed by a rotary evaporator, and the residue was purified through column chromatography (eluent: PE/EA 1:1) to afford 15 (0.658 g, 95%) as a white solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With 3-(ethoxycarbonyl)-1-(5-methyl-5-(nitrosooxy)hexyl)pyridin-1-ium bis(trifluoromethanesulfonyl)imide at 20℃; for 2h; Ionic liquid; | General procedure for the synthesis of products (1b-30b) General procedure: To a Schlenk tube were added arene (1 mmol) and TS-N-IL (1.3 mmol). Then the tube was stirred at room temperature under air for the indicated time until complete consumption of starting material as monitored by TLC analysis. After the reaction was finished, the reaction mixture was extracted with ethyl acetate (3 20 mL). The combined extracts were washed with aqueous NaHCO3, dried over anhydrous Na2SO4 and evaporated in a rotary evaporator under reduced pressure. The crude product was purified by filtration through a column chromatography on silica gel employing ethyl acetate-hexane mixture to afford the desired product. The purity of the compound was confirmed by NMR and mass analysis, vide infra. |
80% | With sulfuric acid; nitric acid at 0℃; | 1 Methyl 3-methoxybenzoate (83.0 g, 500 mmol) in H2S04 (70 wt%, 200 ml) at 0 °C HN03 (65 wt%, 40 ml) was added dropwise and the resulting mixture was stirred overnight before being poured into ice water. The mixture thus obtained was filtered and the solid cake obtained was washed with water (3×300 ml) to give 84.4 g of methyl 4-nitro-3-methoxybenzoate as a yellow solid in a yield of 80%. A solution of methyl 4-nitro-3-methoxybenzoate (84.4 g, 400 mmol) in ethanol (1500 ml) was stirred in the presence of Pd on carbon (10 % Pd, 5.35 g) under H2 atmosphere 5 Hours later, the reaction was filtered through Celite Celite to remove the catalyst. The solvent was evaporated under vacuum to give an off-white solid. The off-white solid was recrystallized from methanol to give methyl 4-amino-3-methoxybenzoate. (70.95 g, 392 mmol), yield 98%. |
80% | With sulfuric acid; nitric acid at 0℃; | 1 Example 1: Synthesis of intermediate 4-amino-3-methoxybenzoic acid methyl ester To a solution of methyl 3-methoxybenzoate (83.0 g, 500 mmol) in H2SO4 (70 wt%, 200 ml) was added HNO3 (65 wt%, 40 ml) dropwise at 0 °C. The resulting mixture was stirred overnight, and then poured into ice water. The mixture thus obtained was filtered, and the solid cake obtained was washed with water (33300 ml) to give 84.4 g of 4-nitro-3methoxybenzoic acid methyl ester as a yellow solid. Yield: 80%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | Stage #1: 2'-allyloxyacetophenone With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.25h; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran; mineral oil for 20h; Reflux; | 1,3 Diketone Procedure 1 General procedure: To a solution of the required 2-hydroxyacetophenone (1 equiv) in DMF at rt, was added allyl bromide (1.1 equiv), K2CO3 (3 equiv) and TBAI (0.1 equiv), and the suspension was stirred for 20 h. The reaction mixture was diluted with water and extracted with ethyl acetate (×3). The combined organic extracts were washed with water (×3) and brine (×1), dried over Na2SO4, and reduced in vacuo to provide the allyl ether in sufficient purity to be used in the next step. To a solution of the 2-(2-propen-1-yloxy)acetophenone derivative (1 equiv) in THF at 0 °C was added NaH (2.5 equiv) with stirring for 15 min. After this time the reaction was warmed to rt, and a solution of the desired ester (1-2 equiv) in anhydrous THF was added. The resulting solution was heated at reflux for a further 20 h. The reaction was quenched with 2 M HCl and extracted with EtOAc (×2). The combined organic extracts were washed with water (×1) and brine (×1), dried, and reduced in vacuo. The residue was of sufficient purity to be used in the next step, but an analytically pure sample could be obtained by subjecting the crude residue to silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With tetrakis(triphenylphosphine) palladium(0); potassium acetate; silver fluoride; CyJohnPhos In hexane at 140℃; for 20h; Inert atmosphere; Sealed tube; | |
58% | With (bis(tricyclohexyl)phosphine)palladium(II) dichloride; iron(II) acetate; potassium carbonate In 1,2-dichloro-ethane at 110℃; for 48h; Schlenk technique; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With oxygen; copper diacetate; caesium carbonate In N,N-dimethyl-formamide at 145℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With (1,5-cyclooctadiene)(methoxy)iridium(I) dimer; 4,4'-di-tert-butyl-2,2'-bipyridine In hexane at 20℃; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
37% | With sodium hydride; In tetrahydrofuran; mineral oil;Reflux; | General procedure: To a suspension of sodium hydride (60% in mineral oil, 5 eq) in dryTHF was added solution of substituted methyl benzoate (2 eq) in dryTHF. After mixture refluxed, substituted acetophenone (1 eq) in dryTHF was added dropwise. The mixture was refluxed overnight, then quenched with 1 N HCl. The mixture was extracted with ethyl acetatetwice, and the combined organic phase was washed with brine solution,dried with anhydrous Na2SO4, filtrated, and concentrated under reduced pressure. The residue was purified on a silica gel column. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With hydrogenchloride; montmorillonite K10 Clay In dichloromethane; water at 45℃; for 4h; Green chemistry; | 1-3 Preparation of acidified montmorillonite: In a 2L round bottom flask, Add montmorillonite (200g) and 3% aqueous hydrochloric acid (1.2L) Heat to 100 ° C and stir for 24 hours. filter, The filter cake was washed with distilled water (1.5 L). It was activated in an oven at 100 ° C for 6 hours. Put it in the desiccator for later use. Preparation of methyl (5-nitro-1-toluenesulfonyl-1H-indol-3-yl)acetate: In a 250 mL round bottom flask, Methyl (5-nitro-1-toluenesulfonyl-1H-indol-3-yl)acetate (19.4 g, 0.05 mol) And methyl 3-methoxybenzoate (8.4 g, 0.05 mol) was dissolved in 100 mL of dichloromethane. Acidified montmorillonite (16.8g) was added with stirring. The reaction was heated to 45 ° C for 4 hours. TLC determines the disappearance of raw materials, Cool to room temperature, let stand, filter, The filtrate was distilled under reduced pressure to remove the organic solvent to give a yellow solid. Recrystallization from ethyl acetate / cyclohexane gave a white solid Methyl 3-methoxy-4-[(5-nitro-1-toluenesulfonyl-1H-indol-3-yl)methyl]benzoate (18.4 g, yield 74%). |
56% | With Montmorillonite In 1,2-dichloro-ethane at 80℃; | 7. Synthesis of compounds 10, 11, 13 and 14 To a solution of 11 (2.8 g, 7.2 mmol) in 1,2-dichloroethane (30 mL) was added 12 (1.4 g, 8.6 mmol) and H-mont (2.2 g). The reaction was stirred at 80 oC under air until completion (monitored by TLC). The reaction mixture was filtered over Celite to remove H-mont, and then washed with 1,2-dichloroethane (10 mL). The filtrate was evaporated to dryness, and the residue was purified by flash chromatography (petroleum ether/ethyl acetate, 15:1) to give 13 as a white solid (2.0 g, 56 % yield). 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 2.0 Hz, 1H), 8.17 (dd, J = 9.1, 2.1 Hz, 1H), 8.03 (d, J = 9.1 Hz, 1H), 7.72 (d, J = 8.3 Hz, 2H), 7.55 (dd, J = 3.7, 2.7 Hz, 2H), 7.41 (s, 1H), 7.24 (d, J = 6.1 Hz, 2H), 7.10 (d, J = 8.1 Hz, 1H), 4.04 (s, 2H), 3.91 (s, 3H), 3.90 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 166.9, 157.0, 145.9, 144.1, 138.2, 134.7, 132.2, 130.8, 130.2, 129.8, 126.9, 126.7, 122.3, 122.2, 120.0, 116.5, 113.9, 111.3, 55.7, 52.3, 25.4, 21.8; ESI MS m/z 517.1 [M + Na]+; HRMS calcd for C25H22N2O7SNa [M + Na]+ m/z 517.1045, found 517.1056. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: methyl 3-methoxybenzoate With ammonia; lithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 2-bromoallyl bromide In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Further stages; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
36% | With lithium hexamethyldisilazane In tetrahydrofuran at 0 - 25℃; for 16h; | 45-a (Example 45-a) 2-(5-Bromopyridin-2-yl)-1-(3- methoxyphenyl) ethan-1-one To a solution of methyl 3-methoxybenzoate (1.93 g,11.6 mmol) and 5-bromo-2-methyl-pyridine (2.0 g,11.6 mmol) in THE (20 mL) was added LiHMDS (1 M, 11.6 mi,11.6 rnmol) at 0°C. The mixture was stirred at 25°C for16 h. The reaction mixture was quenched by addition saturate NH4C1 solution (30 mL) and extracted with EtOAc (20 mL x 3) . The combined organic phase was washed with brine (30 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue.The residue was purified by column chromatography on silica gel (PE/EtOAc=0 to 20:1) to give the title compound (1.35 g, 4.19 mmol, yield: 36.0%) as an oil. LCMS (ES) : m/z 305 [M+H. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitric acid; In water; at 20℃; | 3-hydroxybenzoic acid (Acros) 4 (1.38 g) was dissolved in 40 mL acetone, then K2CO3 (3.0 g) and dimethyl sulfate (2.7g) were added in one portion. The mixture was heated to reflux for 1-2 hours until 4 was completely consumed (monitored by TLC). Then the reaction mixture was cooled down to room temperature. The reaction mixture was passing through a short pad of silica gel to remove K2CO3, and 200 mL acetone was used subsequently to wash the residue. The clear filtration was condensed under vacuum to give a syrup-like residue, which was dissolved in 15 mL HNO3 (68-70% in aqueous as received) at room temperature. The solution was well stirred overnight until the starting material was consumed (monitored by TLC). Compound 5 was precipitated out from the solution (nitration by-products 5a and 5b were still in the solution and were recovered by extraction with CH2Cl2). Simple filtration will afford 5, which was recrystallized from MeOH or EtOAc/Hexane to give large colorless square crystals as pure product in about 50-60% yield. 1H NMR (300 MHz, CDCl3): 7.58 (1H, dd, J = 1.2 Hz, J = 7.2 Hz), 7.47 (1H, tri, J = 8.1 Hz), 7.24 (1H, dd, J = 1.2 Hz, J = 8.1 Hz), 3.90 (3H, s), 3.87 (3H, s). 13C NMR (75 MHz, CDCl3): 163.4, 150.9, 130.8, 123.6, 122.1, 117.1, 56.8, 52.9. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88.1% | Stage #1: methyl 3-methoxybenzoate With trimethylaluminum In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: 2-amino-3,5-dibromopyrazine In tetrahydrofuran at 60℃; for 1.5h; | A Step A: N- dibromopyrazin-2-yl )-6-methoxypi col inamide To a solution of 3,5-dibromopyrazin-2-amine (13.6g, 54mmol, 1.3 equiv) in THF was added AlMe3 (1.6 mol/L, 34 mL, 54 mmol, 1.3 equiv) dropwise at room temperature under argon atmosphere. The mixture was stirred at room temperature for 0.5 h. Then 3,5- dibromopyrazin-2-amine (6.8 g, 4lmmol, 1.0 equiv) was added in one portion. The mixture was stirred at 60°C for 1.5 h, quenched with 1N HC1 (aq.) and extracted with ethyl acetate for three times. The extracts were washed with brine, dried over anhydrous Na2S04 and concentrated in vacuo. The residue was purified by column chromatography on silica gel to afford the title compound N-(3,5-dibromopyrazin-2-yl)-6-methoxypicolinamide as a yellow solid (l4g, 88.1% yield). LC-MS: m/z 386.8, 388.8, 390.8 (M+H) + |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With lithium hexamethyldisilazane In tetrahydrofuran at 60℃; for 12h; Inert atmosphere; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With sodium hydride In tetrahydrofuran; mineral oil at 60℃; for 24h; High pressure; Cooling with ether-dry ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With sodium hydride In tetrahydrofuran; mineral oil at 60℃; for 24h; High pressure; Cooling with ether-dry ice; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With lithium diisopropyl amide In tetrahydrofuran; hexane at -20 - 20℃; Inert atmosphere; | |
With n-butyllithium In tetrahydrofuran at -78 - 0℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | Stage #1: N,N-dimethyl-2-phenylacetamide With lithium diisopropyl amide In tetrahydrofuran at -78℃; for 2h; Inert atmosphere; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at -78 - 20℃; for 12h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With N-iodo-succinimide; 1,10-Phenanthroline; oxygen; potassium carbonate; copper dichloride In dimethyl sulfoxide at 140℃; for 24h; Molecular sieve; | General procedure for aerobic esterification General procedure: In a typical experiemnt, 0.2 mmol alcohol substrate, 100 μL MeOH, 0.08 mmol CuCl2 ,0.08 mmol phen, 0.4 mmol NIS, 1 mmol K2CO3, 100 mg 4Å, 0.2 mmol n-decane asinternal standard, and 2 mL DMSO were added into a Teflon-lined stainless-steelreactor, followed by chaging 0.5 MPa O2. Then the mixture was heated to 140 °C for adesired period of time. After reaction, the reactor was quenched in ice-water bath,followed by addition of sodium hyposulfide, and extraction using ethyl acetate andsaturated aqueous NH4Cl to separate the products. Subsequently, the organic matterwas extracted with ethyl acetate twice, and combined for qualitative and quantitativeanalysis. For aerobic oxidative conversion of eucalyptus lignin, 40 mg eucalyptus lignin, 100 μLMeOH, 0.08 mmol CuCl2 , 0.08 mmol phen, 0.4 mmol NIS, 1 mmol K2CO3, 100 mg4Å, and 2 mL DMSO-d6 were added into a Teflon-lined stainless-steel reactor, followedby charging 5 MPa O2. After reaction, the reaction mixture was concentrated in vacuoto remove the excess MeOH before 2D Short-range 13C-1H correlation (HSQC)measurement. |
93 %Chromat. | With oxygen; potassium carbonate at 150℃; for 24h; Autoclave; | |
96 %Chromat. | With oxygen; potassium carbonate at 130℃; for 12h; Autoclave; | 9 Example 9 Add Co-NC (5mol%), 1-(3-methoxyphenyl)-1-ethanol (1mmol), K2CO3 (20mol%), and 4mL methanol to a 25mL polytetrafluoroethylene lined autoclave. , Airtight the reactor, fill with oxygen pressure to 0.4MPa, put the reactor into an oil bath at 130°C, stir for 12h at 400 speed, after the reaction, cool the reactor to room temperature, open the reactor, and add the internal standard biphenyl (60mg), the qualitative product is detected by gas chromatography-mass spectrometry, and the yield of the substrate 1-(3-methoxyphenyl)-1-ethanol and the product methyl 3-methoxybenzoate is determined by the gas chromatography internal standard method. Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With potassium carbonate; potassium iodide at 20℃; for 12h; | 3.1 1) Synthesis of methyl 3-methoxybenzoate: At room temperature, 3-hydroxybenzoic acid (3g, 21.74mmol) was dissolved in dry N,N-dimethylformamide (DMF) (20ml), potassium carbonate (9g, 65.22mmol) and potassium iodide ( 3ml, 47.83mmol), react at room temperature for 12h, and monitor the end of the reaction by TLC. After the reaction was completed, ethyl acetate (20ml) was added, washed with saturated ammonium chloride aqueous solution (10ml) and distilled water (10ml), the aqueous phase was extracted with ethyl acetate, the organic phases were combined, and dried over anhydrous sodium sulfate. The solvent was removed with a rotary evaporator, and purified by silica gel column chromatography (petroleum ether: ethyl acetate = 12:1) to obtain 3.43 g of white solid methyl 3-methoxybenzoate with a yield of 95%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate In acetonitrile at 50℃; for 12h; | General synthetic procedure for intermediates 13a-o. General procedure: Step 1: Phenol derivative (1.0 equiv) and halohydrocarbons (1.0 equiv) were dissolved in acetonitrile (15 mL) and K2CO3 (3.0 equiv) was added and heated to 50 °C for 12 h and then cooled to room temperature. The mixture was filtered with celite and the filter cake was washed with ethyl acetate and then evaporate the solvent in vacuo to give the crude. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In acetonitrile at 20℃; for 3h; | Phenyl(p-tolyl)iodonium(III) trifl ate (3a). General procedure: To a stirred solution of equimolar amounts of toluene 2a (46 mg, 0.50 mmol) and PhI(OAc)2 (1a) (161 mg, 0.50 mmol) in MeCN (2 mL), a solution of trifl uoromethanesulfonic acid (~150 mg, 1.0 mmol, 2 equiv.) in MeCN (1 mL) was added dropwise at room temperature. The resulting clear solution was stirred for 3 h, then methanol (~2 mL) was added, and the solvents were removed under reduced pressure. The residue was treated with diethyl ether with stirring for precipitation of iodonium(III) triflate 3a. The precipitate was filtered and dried in vacuo to give a pure iodonium(III) salt 3a as a white powder. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | With sodium borodeuteride; d(4)-methanol at 60℃; for 36h; | 1 To a solution of methyl 3-methoxybenzoate (0.4 g, 2.4 mmol) in methan-d3-ol-d (4 mL) was added sodium borodeuteride (0.5 g, 12 mmol, 99% D) at ambient temperature and the solution was heated to 60 °C for 36 hours. The reaction mixture was cooled to ambient temperature and concentrated in vacuo to give a crude residue. The crude residue was quenched with water and extracted with ethyl acetate. The organic layer was washed with water, brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The crude material was purified by flash chromatography (15% ethyl acetate/hexane) to provide (3- methoxyphenyl)methan-d2-ol as a colorless liquid (0.15 g, 45% yield): 1H NMR (400 MHz, CDCl3) d 7.29 (s, 1H), 6.44 (d, J = 6.4Hz, 2H), 6.83-6.85 (m, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | General procedure: A 15 mL Schlenk tube equipped with a stirrer bar was chargedwith CuCl (10 mol%), L7 (13 mol%), LiOMe (2.5 equiv), and theappropriate boronic ester 1 or 4 (0.375 mmol). The vessel wasthen evacuated and filled with Ar (three cycles). DMA (0.5 mL)and (Boc)2O (0.25 mmol) were added sequentially under Ar, andthe mixture was stirred at 30 for 6 h. MeI (5 equiv) was thenadded in air, and the mixture was stirred at 30 for additional2 h. The mixture was finally diluted with EtOAc and washedwith sat. aq NaCl (20 mL). The aqueous phase was furtherextracted with EtOAc (3 × 20 mL), and the combined organicphases were dried (Na2SO4) and concentrated. The residue waspurified by column chromatography [silica gel EtOAc-hexane(1:100 to 1:50)]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: methyl 2-bromo-5-methoxybenzoate With nickel(II) iodide; 1,4-bis(dicyclohexylphosphino)butane; sodium carbonate; cesium iodide In tetrahydrofuran for 0.25h; Schlenk technique; Glovebox; Stage #2: In tetrahydrofuran at 35℃; for 72h; Irradiation; | General Procedure A (solid aryl bromides). General procedure: An oven dried Schlenk tube containing a stir barwas charged with arylbromide (0.2 mmol), Na2CO3 (0.3 mmol, 31.8 mg, 1.5 equiv), and NiI2(0.02 mmol, 6.1 mg, 10 mol%). The Schlenk was transferred to a nitrogen filled gloveboxwhere dcyb (0.022 mmol, 9.9 mg, 11 mol%), CsI (0.04 mmol, 10.4 mg, 20 mol%), andanhydrous THF (0.2 M, 1 mL) was added. The Schlenk was sealed and the mixture was stirredfor 15 minutes. It was taken out of the glovebox and placed in a preheated reaction vessel at 35C (see pictures) and stirred for 72 hours under blue light irradiation. The mixture was quenchedwith 1M HCl (2 mL) and extracted with EtOAc, 0.5 cm3 of silica gel was added to the roundbottom flask and evaporated on a rotary evaporator set at 40 C and 100 mbar. The silica wasthen subjected to column chromatography |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,5'-dihydroxy acetophenone With lithium hexamethyldisilazane In tetrahydrofuran at -78℃; for 3h; Inert atmosphere; Heating; Stage #2: methyl 3-methoxybenzoate In tetrahydrofuran at -78 - 20℃; Inert atmosphere; | 5.2 General procedure for the synthesis of 5a-d General procedure: A solution of LiHMDS in THF (1M, 4 equiv) was added to a well-stirred solution of 2,5-dihydroxyacetophenone (2, 1 equiv) in anhydrous THF (20mL) under argon at -78°C over 15min. The reaction mixture was stirred at -78°C for 1h and at -10°C for 2h and was cooled again to -78°C, and a solution of 3a-d (1 equiv) in THF (5mL) was added in one portion. The mixture was stirred at -78°C for 1h and at room temperature overnight. The reaction mixture was poured into a mixture of ice and neutralized with concentrated HCl (6.5mL) and extracted with dichloromethane. The combined organic layer was washed with brine and dried over sodium sulfate, filtered, and evaporated to give crude 4a-d. Crude 4a-d were dissolved in glacial acetic acid (20mL) and concentrated sulfuric acid (0.2mL). The reaction was stirred at room temperature for 4h. H2O (20mL) was added to the reaction mixture, and the resulting solid was filtered, washed with water, and dried to afford 5a-d. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With N<SUP>1</SUP>-(4-hydroxy-2,6-dimethylphenyl)-N<SUP>2</SUP>-(4-hydroxy-3,5-dimethylphenyl)oxalamide; caesium carbonate; copper(I) bromide In 1-methyl-pyrrolidin-2-one; hexane at 80℃; for 12h; Inert atmosphere; Schlenk technique; Sealed tube; |
Tags: 5368-81-0 synthesis path| 5368-81-0 SDS| 5368-81-0 COA| 5368-81-0 purity| 5368-81-0 application| 5368-81-0 NMR| 5368-81-0 COA| 5368-81-0 structure
[ 19520-74-2 ]
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