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CAS No. : | 4744-08-5 | MDL No. : | MFCD00009245 |
Formula : | C7H16O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | MBNMGGKBGCIEGF-UHFFFAOYSA-N |
M.W : | 132.20 | Pubchem ID : | 20858 |
Synonyms : |
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 1.0 |
Num. rotatable bonds : | 5 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 37.93 |
TPSA : | 18.46 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) : | -5.89 cm/s |
Log Po/w (iLOGP) : | 2.44 |
Log Po/w (XLOGP3) : | 1.72 |
Log Po/w (WLOGP) : | 1.8 |
Log Po/w (MLOGP) : | 1.36 |
Log Po/w (SILICOS-IT) : | 1.32 |
Consensus Log Po/w : | 1.73 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.41 |
Solubility : | 5.1 mg/ml ; 0.0386 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.72 |
Solubility : | 2.5 mg/ml ; 0.0189 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.75 |
Solubility : | 2.35 mg/ml ; 0.0178 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.16 |
Signal Word: | Danger | Class: | 3 |
Precautionary Statements: | P210 | UN#: | 1989 |
Hazard Statements: | H225 | Packing Group: | Ⅱ |
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 |
---|---|---|
With hydrogenchloride; benzene |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With quinoline; toluene-4-sulfonic acid | ||
With kaolin at 300 - 450℃; | ||
With kaolin asbestos sodium silicate at 340 - 350℃; |
With sodium trisilicate; magnesium hydrogen phosphate at 320℃; | ||
With quinoline; toluene-4-sulfonic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.5% | 2 Into a 500 ml flask equipped with a 12 packed column were added 0.25 g (0.0013 moles) of p-toluene sulfonic acid, followed by 241 g (1.82 moles) of 1. Nitrogen was bubbled into the mixture while 0.157 g (0.00065 moles) of bis(2-ethylhexyl)amine were added. The nitrogen flow was reduced, and the mixture was distilled to 160 C. to partially remove ethyl alcohol and 1-ethoxy-1-propene. The reaction mixture washed with 320 ml of water and then with 70 ml of water. The organic layer was dried over magnesium sulfate and filtered to produce 121 g (77.5%) of 2, bp 67-76 C., as a clear, colorless liquid. Gas chromatographic analysis showed less than 0.01% ethylvinyl ether. | |
75% | With quinoline; phosphorus pentoxide distillation at a bath temp. 150 deg C; | |
With quinoline; phosphorus pentoxide vermutlich entsteht als Gemisch von cis- und trans-Form; |
With sodium hydrogen sulfate vermutlich entsteht als Gemisch von cis- und trans-Form; | ||
With silver-asbestos at 280℃; vermutlich entsteht als Gemisch von cis- und trans-Form; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With N-Bromosuccinimide; at 50℃; for 0.166667h;Irradiation; | 500 grams of propionaldehyde diethyl acetal,Add a small amount of NBS and heat to 50 C.Under the illumination of 200W tungsten lamp,Until the orange color disappears and the ice water cools down,The remaining 672 grams of NBS was added in portions. After the addition, continue to react for 10 minutes.The mixture is filtered,The solid was separated and washed twice with chloroform and the filtrate was collected.After the filtrate was evaporated to dryness under reduced pressure, the residue was evaporated to dryness to give a fraction of 78-86 C / 22 mmHg. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.6% | With zirconium(IV) sulfate at 90℃; Flow reactor; | 1-6; 1-4 Example 5 Fill 30g of zirconium sulfate evenly in the middle part of the 50cm rectification tower, weigh 690g of ethanol into a 1000mL reactor, turn on the stirring, heating and low-temperature circulating water cooling pump, control the reaction temperature in the reactor to 90°C, add 435g of propionaldehyde dropwise to the reactor at a uniform rate, and control the dripping rate of propionaldehyde to 5g/min. The crude product is extracted from the bottom of the tower at a rate of about 11.7g/min. The content of 1,1-diethoxypropane after mixing the extracted materials is 54.7%. After rectification, the content of 1,1-diethoxypropane is 99.4%. 1,1-diethoxypropane, the yield is 98.6%, and the fraction before rectification is directly used. The unreacted raw materials are recycled and reused after membrane dehydration. |
78.8% | With calcium chloride at 25 - 35℃; for 10h; | 1.1 1) Synthesis of propionaldehyde diethyl acetal Take 1000ml three bottles,Add anhydrous ethanol 300g and anhydrous calcium chloride 75g,Control 25 ~ 35 dropping propionaldehyde 150g,The reaction was complete after incubation for 10 hours,The crude product 360g, content of 85% to 87%Crude product obtained after rectification acetal diethyl acetal 280g, The content of 95 ~ 97%, the yield of 78.5% ~ 78.8%. |
With hydrogenchloride |
With hydrogenchloride at 25℃; Gleichgewicht der Reaktion; | ||
With hydrogenchloride | ||
With activated bauxit | ||
With aluminium-diethylate chloride | ||
With calcium chloride | ||
With sulfuric acid at 58℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81.6% | With ammonium nitrate In ethanol at 20 - 36℃; | 1 Into a 2-liter flask under nitrogen were added 586 g (3.96 moles) of triethyl orthoformate, 46 g (56 ml, 1 mole) of ethanol, and 16 g of ammonium nitrate. Over the course of one hour 232 g (4 moles) of propionaldehyde were added with stirring. An ice bath was used as necessary to keep maintain the mixture at 30-360C. The mixture turned yellow orange after one-third of the propionaldehyde had been added. The mixture was stirred overnight at room temperature and then brought to pH 7.5 +/-0.2 with 10% aqueous sodium carbonate (about 30 ml). The aqueous layer was decanted, and the organic layer was distilled over sodium carbonate at atmospheric pressure to produce 124 g (81.6%) of 1. |
81.6% | Stage #1: propionaldehyde; orthoformic acid triethyl ester With ammonium nitrate; ethanol at 20 - 36℃; Stage #2: With sodium carbonate In water at 20℃; | 1 Into a 2-liter flask under nitrogen were added 586 g (3.96 moles) of triethyl orthoformate, 46 g (56 ml, 1 mole) of ethanol, and 16 g of ammonium nitrate. Over the course of one hour 232 g (4 moles) of propionaldehyde were added with stirring. An ice bath was used as necessary to keep maintain the mixture at 30-36 C. The mixture turned yellow orange after one-third of the propionaldehyde had been added. The mixture was stirred overnight at room temperature and then brought to pH 7.5 with 10% aqueous sodium carbonate (about 30 ml). The aqueous layer was decanted, and the organic layer was distilled over sodium carbonate at atmospheric pressure to produce 124 g (81.6%) of 1. |
With sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | at 10 - 15℃; | |
61% | at 0 - 25℃; for 0.5h; | |
With iron(III) chloride |
With iron(III) chloride | ||
With boron trifluoride diethyl etherate at 65℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diethyl ether Hydrolyse mit verduennter Essigsaeure und sofortige Neutralisation; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With trifluorormethanesulfonic acid In dichloromethane for 0.25h; Heating; | |
With sulfuric acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | In diethyl ether at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With boron trifluoride diethyl etherate In dichloromethane at -75℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | at 25℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With dibutyltin chloride In water at 20℃; for 0.333333h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With triphenylmethyl perchlorate In dichloromethane at -60℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 49% 2: 33% | With 4 A molecular sieve; toluene-4-sulfonic acid In toluene; Petroleum ether for 24h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With toluene-4-sulfonic acid In 1,4-dioxane Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With trimethylsilylazide for 12h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With titanium tetrachloride In dichloromethane for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With trimethylsilyl trifluoromethanesulfonate In dichloromethane at -78℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trichlorophosphate 1.) <30 deg C, 2.) 70 deg C, 2 h; Yield given. Multistep reaction. Yields of byproduct given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | In dichloromethane at -20 - 20℃; | |
78% | In hexane at 35 - 40℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
11.8% | With boron trifluoride diethyl etherate In dichloromethane for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With water In tetrahydrofuran at -78 - 20℃; for 2h; | |
80% | With water In tetrahydrofuran at -78 - 20℃; for 2h; also other electrophiles (D2O, (PhCH2)2S2, n-C3H7CHO, PhCHO, n-C7H15CHO, PhCH=NPh); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With toluene-4-sulfonic acid for 24h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With trimethylsilyl trifluoromethanesulfonate In dichloromethane for 6h; Ambient temperature; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With trimethylsilyl trifluoromethanesulfonate In acetonitrile at -45℃; for 3h; Yield given; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid at 23℃; for 24h; Yield given. Yields of byproduct given. Title compound not separated from byproducts; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With perchloric acid; acetic anhydride In dichloromethane at -15 - -5℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With triethylsilane; trifluoroacetic acid In acetonitrile at 22℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
42% | Stage #1: 1,1-diethoxypropane; N,N-bis(trimethylsilyloxy)-1-propen-2-amine With pyridine; trimethylsilyl trifluoromethanesulfonate In dichloromethane at -78℃; for 17h; Stage #2: With N-benzyl-N,N,N-triethylammonium chloride In dichloromethane at -78℃; for 0.0833333h; Stage #3: With acetic acid; triethylamine In methanol; dichloromethane at -78 - 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
40% | Stage #1: 1,1-diethoxypropane; N,N-bis(tert-butyldimethylsilyloxy)prop-1-en-2-amine With pyridine; trimethylsilyl trifluoromethanesulfonate In dichloromethane at -78℃; for 17h; Stage #2: With N-benzyl-N,N,N-triethylammonium chloride In dichloromethane at -78℃; for 0.0833333h; Stage #3: With acetic acid; triethylamine In methanol; dichloromethane at -78 - 20℃; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: propionaldehyde; 3-(dimethylphenylsilyl)-5-phenyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-pentene With titanium tetrachloride In dichloromethane at -78℃; for 2h; Stage #2: 1,1-diethoxypropane In dichloromethane at 0℃; for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With titanium tetrachloride In dichloromethane at -78℃; for 3h; | |
99% | With titanium tetrachloride In dichloromethane TiCl4, CH2Cl2, -78°C, 3 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With titanium tetrachloride In dichloromethane at -78℃; for 3h; | |
94% | With titanium tetrachloride In dichloromethane TiCl4, -78°C, CH2Cl2, 3 h; | |
82% | With aluminium trichloride In dichloromethane AlCl3, CH2Cl2, -78°C, 0.5 h; -20°C for 2.5 h; |
30% | With trimethylsilyl trifluoromethanesulfonate In dichloromethane TMSOTf, CH2Cl2, -78°C, 0.5 h; -20°C for 2.5 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With titanium tetrachloride In dichloromethane at -78℃; for 3h; | |
95% | With titanium tetrachloride In dichloromethane TiCl4, CH2Cl2, -78°C, 3 h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Stage #1: 1,1-diethoxypropane; N,N-dimethyl-formamide With trichlorophosphate In N,N-dimethyl-formamide at 70℃; for 2h; Stage #2: urea With sodium In ethanol for 48h; Heating; | |
Multistep reaction; | ||
9 g | Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 30℃; Stage #2: 1,1-diethoxypropane at 40 - 70℃; for 2h; Stage #3: urea With sodium In ethanol for 48h; Reflux; | 52B Example 52B At 0°C, DMF (62mL) was dropwise added slowly to vigorously stirred phosphorus oxychloride (64mL) below30°C. After heated to 40°C, the reaction solution was slowly added with 1,1-diethoxypropane (53mL, 307.9mmol) withthe temperature kept between 60°C to 70°C, and then the dark brown reaction solution was heated to 70°C and stirredfor 2 hours. After cooled to room temperature, the mixture was poured to ice water and kept overnight, then adjusted topH = 9 with anhydrous potassium carbonate. The aqueous layer was extracted with dichloromethane, the organic layerwas dried and concentrated in vacuo to give the title compound as a liquid (15g, crude mixture).; Sodium (12.2g, 530.3mmol) was added to absolute ethanol (200mL) at room temperature and the mixture wasstirred until sodium disappeared. Then, a solution of (E)-3-ethoxy-2-methylacrolein and (E)-3-(dimethylamino)-2-methylacrolein(15g, 134mmol) in ethanol (100mL) and urea (9.6g, 159mmol) were added, the mixture was stirred underreflux for 2 days. The reaction solution was adjusted to pH = 9 and continued to reflux overnight, and then concentratedin vacuo. The residue was purified by column chromatography to give the title compound (9g). 1H NMR (400 MHz,DMSO-d6) ppm 7.92-8.14 (m, 2H), 2.52 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In dichloromethane at 0 - 20℃; for 5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | Stage #1: acetophenone With di-n-butylboryl trifluoromethanesulfonate; N-ethyl-N,N-diisopropylamine In dichloromethane at -78℃; for 0.5h; Stage #2: 1,1-diethoxypropane In dichloromethane at -78℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57% | With toluene-4-sulfonic acid In N,N-dimethyl-formamide at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With trichlorophosphate at 70℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
33% | With boron trifluoride diethyl etherate In dichloromethane at 20℃; for 4h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 31% 2: 22% 3: 14% | In 1,2-dichloro-ethane at 100℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 1,1-diethoxypropane; N,N-dimethyl-formamide With trichlorophosphate In N,N-dimethyl-formamide at 70℃; for 2h; Stage #2: With water; potassium carbonate Title compound not separated from byproducts; | ||
Stage #1: N,N-dimethyl-formamide With trichlorophosphate at 0 - 30℃; Stage #2: 1,1-diethoxypropane at 40 - 70℃; for 2h; | 52A Example 52A At 0°C, DMF (62mL) was dropwise added slowly to vigorously stirred phosphorus oxychloride (64mL) below30°C. After heated to 40°C, the reaction solution was slowly added with 1,1-diethoxypropane (53mL, 307.9mmol) withthe temperature kept between 60°C to 70°C, and then the dark brown reaction solution was heated to 70°C and stirredfor 2 hours. After cooled to room temperature, the mixture was poured to ice water and kept overnight, then adjusted topH = 9 with anhydrous potassium carbonate. The aqueous layer was extracted with dichloromethane, the organic layerwas dried and concentrated in vacuo to give the title compound as a liquid (15g, crude mixture). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With 10-camphorsufonic acid In dichloromethane at 55℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: 2) DBU / 1) pentane, 25 to 30 deg C, 5 min, 2) pentane, THF, HMPA, RT 3: 1) m-CPBA (80-85percent), 2) Et3N / 1) CH2Cl2, -78 to 0 deg C then 1 h at 0 deg C, 2) CH2Cl2, pentane, reflux; var.reag.: H2O2 in pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: pentane / 0.08 h / 25 - 30 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 3 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: 2) DBU / 1) pentane, 25 to 30 deg C, 5 min, 2) pentane, THF, HMPA, RT 3: 1) m-CPBM (80-85percent), 2) Et3N / 1) CH2Cl2, -78 to 0 deg C then 1 h at 0 deg C, 2) CH2Cl2,pentane, reflux; var. reag.: H2O2 in pyridine |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: 2) DBU / 1) pentane, 25 to 30 deg C, 5 min, 2) pentane, THF, HMPA, RT |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: 2) DBU / 1) pentane, 25 to 30 deg C, 5 min, 2) pentane, THF, HMPA, RT |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 75 percent / P2O5, quinoline / distillation at a bath temp. 150 deg C 2: 2) DBU / 1) pentane, 25 to 30 deg C, 5 min, 2) pentane, THF, HMPA, RT |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; In triethylamine; at 20℃; for 3h; | To a solution of 2.36 g (8.0 mmol) of <strong>[25245-29-8]1-iodo-3,4,5-trimethoxybenzene</strong>(2) in triethylamine (80 ml) were added 1.38 ml (9.6 mmol) of 3,3-diethoxy-1-propane, 56 mg (0.080 mmol) of bis(triphenylphosphine)palladium (II) chloride and 8.0 mg (0.040 mmol) of cuprous iodide with stirring under nitrogen, and the mixture was stirred for 3 hours at room temperature. Insoluble materials were removed from the reaction mixture by suction filtration through Celite, and the filtrate was concentrated under reduced pressure. The resultant crude oil was purified by column chromatography on silica gel to obtain 2.29 g (yield: 97%) of 1,1-diethoxy-3-(3,4,5-trimethoxyphenyl)-2-propyne as colorless needles (melting point: 62.5-63.0 C.). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
32% | With piperidine; copper(l) iodide;bis(acetato)bis(triphenylphosphine)palladium(0); In DMF (N,N-dimethyl-formamide); at 20 - 45℃; | A dried flask under nitrogen is charged with <strong>[157942-12-6]methyl 3-hydroxy-4-iodobenzoate</strong> (10.0 g, 35.9 mmol), propioaldehyde diethyl acetal (5.72 ml, 40.0 mmol), bistriphenylphosphine palladium diacetate (538 mg, 0.72 mmol), copper iodide (273 mg, 1.4 mmol) and piperidine (3.94 ml, 40.0 mmol) in DMF (50 ml). The mixture is stirred at 45 C. for 6 h, then at RT overnight. The reaction is diluted with EtOAc (250 ml) and washed with 50% saturated 1:1 NaCl/NaHCO3 solution (4×100 ml). The organic layer is dried (Na2SO4), filtered and concentrated to a brown oil. The crude material is chromatographed over 500 g slurry-packed silica, eluting with 15% EtOAc/hexane. The appropriate fractions are collected and concentrated, affording 3.22 g (32%) of methyl 2-(diethoxymethyl)-1-benzofuran-6-carboxylate as an orange oil. 1H NMR (400 MHz, CDCl3): delta1.29, 3.72, 3.96, 5.70, 6.88, 7.61, 7.95, 8.20 ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
48% | With piperidine; copper(l) iodide;bis-triphenylphosphine-palladium(II) chloride; In DMF (N,N-dimethyl-formamide); at 20 - 60℃; | Methyl 4-hydroxy-3-iodo-benzoate (9.9 g, 35 mmol) is combined with propioaldehyde diethylacetal (5.6 ml, 39 mmol), bis(triphenylphosphine)palladium(II) chloride (523 mg, 0.7 mmol), cuprous iodide (266 mg, 1.4 mmol), and piperidine (3.9 ml, 39 mmol) in DMF (50 ml) in a dry flask under nitrogen. The reaction is warmed to 60 C. for 6 h and is stirred overnight at RT. The mixture is diluted with EtOAc (250 ml) and is washed with 2:1:1:0.1 water/brine/saturated NaHCO3/conc. NH4OH (4×100 ml). The organic layer is dried (MgSO4) and is concentrated in vacuo to a dark oil. The crude material is chromatographed over 300 g silica gel (230-400 mesh), eluting with 15% EtOAc/hexane. The appropriate fractions are combined and concentrated to afford 5.2 g (48%) methyl 2-(diethoxymethyl)-1-benzofuran-5-carboxylate as an amber oil. HRMS (EI) calcd for C15H18O5: 278.1154, found 278.1156 (M)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine;palladium diacetate; copper(l) iodide; triphenylphosphine; at 20℃; for 3h; | Compound 14c (R9 = 2,2-difluoroethyl) is prepared using the methods described in general Method R. [[0378]] To a dry flask were added compound 14a (1.4 g, 5. 32 mmol, 1 equiv),, triphenylphosphine (111.6 mg, 0.43 mmol, 0.08 equiv), copper [(1)] iodide (81 mg, 0.43 mmol, 0.08 equiv), palladium acetate (47.7 mg, 0.21 mmol, 0.04 equiv) and triethylamine (20 mL). The mixture was deaerated with nitrogen, followed by addition of propiolaldehyde diethyl acetyl (1.36 g, 10.65 mmol, 2 equiv). The mixture was stirred at rt for 3 hrs. The solvent was removed under vacuum to give a dark residue. The residue was purified by chromatography to give a yellow oil, compound 14b [(R9 =] 3, [3-DIETHOXY-PROP-1-YNYL)] (1.4 g, 100%). [[0379] 1H] NMR (300 MHz, [CDC13)] 8 8.69 (dd, J= 0.8, 5.0, 1), 8.15 (dd, J= 0.8, 1.4, 1), 7.49 (dd, J= 1.7, 5.0, 1), 5.48 (s, 1), 3.99 (s, 3), 3.82-3. 73 (m, 2), 3.71-3. 62 (m, 2), 1.26 (t, J= 7.2, 6). MS (ESPOS): 264.5 [M + H] +. [[0380]] To a solution of 14b [(R9'=] 3, [3-DIETHOXY-PROP-1-YNYL)] (1.4 g, 5.32 mmol) in methanol (100 mL) was added 10 % palladium on carbon (0.3 g). The mixture was purged and charged with hydrogen (1 atm) and shaken at rt overnight. The palladium was removed by filtration and the filtrate was concentrated to give 14c [(R9=3,] 3-diethoxy propyl) as an oil (1.39 g, 98%). [[0381] IH] NMR (300 MHz, [CDC13)] 8 8.60 (d, J= 5.1, 1), 7.98 (d, J= 0.9, 1), 7.31-7. 28 (m, 1), 4.45 (t, J= 5. 4,1), 3. 98 (s, 3), 3.72-3. 58 (m, 2), 3.52-3. 39 (m, 2), 2.79-2. 72 (m, 2), 1.99-1. 90 (m, 2), 1.22-1. 15 (m, 6). [[0382]] To a mixture of 14c [(R9=3,] 3-diethoxy propyl) (0.68 g, 2.55 mmol) in acetic acid (8 mL) and water (2 mL) was added [CONC.] hydrochloric acid (2 drops). The mixture was stirred at rt overnight and the solvent was removed under high vacuum. The residue was diluted with ethyl acetate, washed with sat. sodium bicarbonate [(LX),] brine [(LX).] The organic layer was dried and concentrated to give [4- (3-OXO-PROPYL)-PYRIDINE-2-CARBOXYLIC] acid methyl ester as a yellow oil (0.27 g, 55 %). [[0383]] To a solution of aldehyde [4- (3-OXO-PROPYL)-PYRIDINE-2-CARBOXYLIC] acid methyl ester (0.27 g, 1.4 mmol, 1 equiv) in DCM (5 [ML)] at-78 C was added DAST (0.91 g, 5.6 mmol, 4 equiv). The mixture was warmed to rt and stirred overnight. The mixture was diluted with dichloromethane (60 mL), washed with sat. aqueous [NAHCO3] [(LX),] dried, and evaporated. The residue was purified by prep. [[0384]] TLC (5% MeOH in DCM) to [4- (3,] 3-difluoro-propyl) -pyridine-2-carboxylic acid methyl ester (137 mg, 45%) [: 1H NMR] (300 MHz, [CDC13)] 8 8.64 (d, J= 5.1, 1), 8.00-7. 98 (m, 1), 7.33-7. 29 (m, 1), 5.85 (dddd, J= 4.1, 4.1, 56.4, 56.4, 1), 3.99 (s, [3),] 2.90-2. 83 (m, 2), 2.28- 2.09 (m, [2) ;] MS (ESPOS): 216.4 [M + H] [+.] [[0385]] To a solution [OF 4- (3,] 3-difluoro-propyl) -pyridine-2-carboxylic acid methyl ester (130 mg, 0.6 mmol) (or compound 14c [(R9] = 2,2-difluoroethyl) prepared in the previous steps) in MeOH (3 [ML)] and water (3 mL) were added conc. [HC1] (0.25 mL, 3.0 mmol, 5 equiv) and platinum oxide (65 [MG).] The mixture was purged and charged with hydrogen (1 atm) and stirred overnight. The platinum oxide was removed by filtration and the filtrate was evaporated to give a clear syrup. To the above residue were added 2N [NAOH] (1.21 mL) and t-butyl alcohol (0.7 mL). The mixture was stirred at rt for 2 hrs. Then di-t-butyl dicarbonate (0.16 g, 0.73 mmol) was added. The mixture was stirred at rt overnight. The solvent was removed under vacuum. The residue was diluted with water (10 mL), was washed with ether (20 mL). The aqueous layer was acidified with 2N [HC1] to pH = 2. [0,] and extracted with ethyl acetate (2x). The combined organic layers were dried and concentrated to give [4- (3, 3-DIFLUORO-PROPYL)-PIPERIDINE-1,] 2- dicarboxylic acid 1-tert-butyl ester as a clear syrup (163 mg, 88 %) [[0386] 1H] NMR (300 MHz, [CDC13)] 8 5.77 (dddd, J= 4.2, 4.2, 56.6, 56.6, 1), 4.34 (t, J= 6.4, 1), 3.62-3. 50 (m, 1), 3. [41-3. 30 (M,] 1), 2.05-1. 96 (m, 1), 1. 92-1.73 (m, 4), 1.70-1. 60 (m, 1), 1.52- 1.32 (m, 3), 1.43 (s, 9); MS (ESPOS): 330.5 [M [+ NA] + ;] MS (ESNEG): 306.5 [M-H]-. [[0387]] To a mixture of the [HC1] salt of compound 2b (Rl=Me, [R2=ME)] (140 mg, 0.49 mmol, 1 equiv) in dry DMF (1.2 mL) at [0 C] was added triethylamine (0.34 mL, 2.43 mmol, 5 equiv), followed by the addition of BSTFA (0.20 mL, 0.74 mmol, 1.5 equiv). The reaction mixture was stirred at [0 C] for 10 minutes, and then was stirred at rt for 50 minutes. To the reaction mixture were added the 4- (3, 3-Difluoro-propyl)-piperidine-1, 2-dicarboxylic acid 1-tert-butyl ester (153 mg, 0.50 mmol, 1.0 equiv) and HATU (235 mg, 0.62 mmol, 1.26 equiv). The reaction mixture was stirred at rt for 3 h. The reaction mixture was evaporated to dryness, taken up in ethyl acetate, washed with 10% citric acid [(LX),] water [(LX),] sat. [NAHC03] [(LX)] and brine. The organic layer was dried over [NA2S04] and evaporated to give a pink syrup ... |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With copper(I) iodide; triphenylphosphine;palladium diacetate; In N,N-dimethyl-formamide; | C10 (3.5 g, 15.8 mmol) is added to a suspension of triphenylphosphine (166 mg, 0.63 mmol) and palladium acetate (71 mg, 0.32 mmol) in 25 mL DMF in dry flask under N2. Propioaldehyde diethyl acetal (2.3 mL, 15.8 mmol), cuprous iodide (120 mg, 0.63 mmol), and piperidine (1.6 mL, 16 mmol), are added successively, and the reaction is stirred 6 h at rt. The mixture is diluted with 125 mL EtOAc, is extracted with 4*50 mL 50% saturated 1:1 NaCl/NaHCO3, and the organic layer is dried over anhydrous Na2SO4 and then filtered. The dried organic layer is concentrated in vacuo to a dark oil. The crude material is chromatographed over 40 g silica gel (Biotage), eluding with 50% EtOAc/hexane. The fractions with the desired compound are combined and concentrated to afford 2-(diethoxymethyl)furo[3,2-c]pyridine (C11) (64% yield). HRMS (FAB) calculated for C12H15NO3+H: 222.1130, found 222.1123 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
28% | With copper(I) iodide In N,N-dimethyl-formamide | 7 Preparation of the Acid: C30 (14 g, 37 mmol), propioaldehyde diethyl acetal (5 g, 39 mmol), bis(triphenylphosphine) palladium diacetate (554 mg, 0.74 mmol), cuprous iodide (282 mg, 1.5 mmol), and piperidine (7.3 mL, 74 mmol) are added to 50 mL DMF in a dry flask under N2. The mixture underwent a vigorous exotherm, is cooled in an ice bath, and the mixture is stirred 6 h at rt. The mixture is diluted with 250 mL EtOAc, is washed with 4*100 mL 50% saturated 1:1 NaCl/NaHCO3, and the organic layer is dried over anhydrous MgSO4, filtered, and is concentrated in vacuo to an amber oil. The crude material is chromatographed over 250 g silica gel (230-400 mesh) eluding with 5% EtOAc/hexane. The fractions with the desired compound are combined and concentrated to afford 5,7-dibromo-2-(diethoxymethyl)furo[2,3-c]pyridine (C31) (28% yield). HRMS (FAB) calculated for C12H13Br2NO3+H: 377.9341, found 377.9330 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With toluene-4-sulfonic acid In toluene | 84.A N-[1-(1H-1,2,3-benzotriazol-1-yl)propyl]-4-chlorobenzamide EXAMPLE 84A N-[1-(1H-1,2,3-benzotriazol-1-yl)propyl]-4-chlorobenzamide A suspension of 4-chlorobenzamide (1.50 g, 9.6 mmol), propionaldehyde diethyl acetal (1.53 g, 11.6 mmol), and benzotriazole (1.15 g, 9.6 mmol) in toluene (35 mL) was treated with p-toluenesulfonic acid (100 mg, 0.53 mmol). The mixture was heated at reflux under Dean-Stark conditions for 16 hours, cooled to ambient temperature, and concentrated to dryness. The crude material was purified by flash chromatography (elution with 40% ethyl acetate/hexanes) to provide 0.860 g of the desired product as a white solid. MS (DCI/NH3) m/z 315 (M+H)+. | |
With toluene-4-sulfonic acid In toluene | 84.A N-[1-(1H-1,2,3-benzotriazol-1-yl)propyl]-4-chlorobenzamide EXAMPLE 84A N-[1-(1H-1,2,3-benzotriazol-1-yl)propyl]-4-chlorobenzamide A suspension of 4-chlorobenzamide (1.50 g, 9.6 mmol), propionaldehyde diethyl acetal (1.53 g, 11.6 mmol), and benzotriazole (1.15 g, 9.6 mmol) in toluene (35 mL) was treated with p-toluenesulfonic acid (100 mg, 0.53 mmol). The mixture was heated at reflux under Dean-Stark conditions for 16 hours, cooled to ambient temperature, and concentrated to dryness. The crude material was purified by flash chromatography (elution with 40% ethyl acetate/hexanes) to provide 0.860 g of the desired product as a white solid. MS (DCI/NH3) m/z 315 (M+H)+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With n-butyllithium | B.7 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,4-diethoxy-1-hydroxybut-2-ynyl)pyrazole Preparation B7 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-(4,4-diethoxy-1-hydroxybut-2-ynyl)pyrazole To a solution of propionaldehyde diethyl acetal (0.0192 g) in anhydrous tetrahydrofuran (2 ml) cooled to -78° C. under an atmosphere of nitrogen was added dropwise n-butyl lithium (621 μl, 2.5M in hexanes) and the mixture was stirred for 10 minutes. 3-Cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-formylpyrazole (0.05 g) was added and stirring continued for 30 minutes. The reaction mixture was poured into water (5 ml) and ether (5 ml). The organic layer was separated, dried (Na2 SO4) and evaporated. The residue was purified by column chromatography on silica gel (5 g) eluted with dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a white foam. NMR(CDCl3): 1.23 (t, 6H), 2.6 (d, 1H), 3.6 (m, 2H), 3.75 (m, 2H), 5.35 (s, 1H), 5.73 (d, 1H), 7.73 (s, 1H), 7,75 (s, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene | P.3.d c d) 26 g of 2RS-2,3-dihydroxy-1-(4-phenoxyphenoxy)propane and 14.5 g of propionaldehydediethyl acetal are dissolved in 30 ml of toluene. 55 mg of the acetalisation catalyst prepared according to Example 3Pc) are added to that mixture, which is stirred at room temperature for 50 hours, yielding 29 g of pure 2R,4S-2-ethyl-4-[(4-phenoxyphenoxy)methyl]dioxolan having an optical purity greater than 90%, in the form of a colourless oily liquid having a refractive index of nD20: 1.5459. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In 1,4-dioxane; aqueous sodium chloride; ethyl acetate; | Example 71 5-Hydroxy-4-methyl-2(5H)-furanone STR82 To a mixture of morpholine hydrochloride (4.56 g) and glyoxylic acid hydrate (4.6 g) in 1,4-dioxane (50 ml) is added sufficient water to make a homogeneous solution. To this solution is added 1,1-diethoxypropane (6.61 g), and the mixture is heated to reflux. The 1,1-diethoxypropane dissolves within a few minutes. The mixture is stirred at reflux for 12 hr, cooled, and concentrated to a viscous gum. This is treated with ethyl acetate (50 ml), and the precipitate of morpholine hydrochloride is filtered. The filtrate is concentrated to a brown oil, which is stirred overnight with 0.1N hydrochloric acid in saturated aqueous sodium chloride (25 ml) to hydrolyze morpholine adducts. The mixture is extracted twice with ether, the ether extracts are washed once with saturated sodium chloride and concentrated, and the residue is distilled in vacuo, providing the title compound as a pale yellow, viscous oil (5.0 g), with NMR spectrum as reported by Pattenden and Weedon, J. Chem. Soc. C, 1984 (1968). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In 5,5-dimethyl-1,3-cyclohexadiene; water | 6 EXAMPLE 6 EXAMPLE 6 A solution of 7.45 g of 2',6'-difluoro-2-(3-pyridyl)acetophenone oxime in 170 ml of xylene is mixed with 8.00 g of diethoxypropane and then heated to 80° C. with stirring. After a clear solution has formed, 0.20 g of pulverised Amberlyst A15 is added and the entire mixture is heated to reflux temperature. After 6 hours, the reaction mixture is subjected to clarifying filtration through Celite and the filtrate is freed of excess solvent at 60° C. in a water jet vacuum. After drying in a high vacuum, 2',6'-difluoro-2-(3-pyridyl)acetophenone O-(1-ethoxy-1-methylethyl)oxime is obtained as an E/Z isomer mixture in the form of a yellow oil. On chromatographic separation on silica gel using n-hexane/ethyl acetate (3:1), the E isomer [1 H-NMR (CDCl3, 200 MHz): 1.428 ppm (s, --C(CH3)2)] is obtained first in the form of slightly yellowish oils. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77.5% | With 2-ethyl-N-(2-ethylhexyl)-1-hexanamine; toluene-4-sulfonic acid at 160℃; Distillation; | 2 (0.0013 moles) of p-toluene sulfonic acid, followed by 241 g (1.82 moles) of 1. Nitrogen was bubbled into the mixture while 0..157 g (0.00065 moles) of bis(2-ethylhexyl)amine EPO were added. The nitrogen flow was reduced, and the mixture was distilled to 160°C to partially remove ethyl alcohol and 1-ethoxy-l-propene. The reaction mixture was washed with 320 ml of water and then with 70 ml of water. The organic layer was dried over magnesium sulfate and filtered to produce 121 g (77.5%) of 2, bp 67-76°C, as a clear, colorless liquid. Gas chromatographic analysis showed less than 0.01% ethylvinyl ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine hydrochloride In aqueous HOAc | 32 3-Methyl-5-(phenylmethoxy)-1H-indol-1-amine The conversion of the above compound to 3-methyl-5-benzyloxyindole was conducted according to the method of Keglevic, et al. [C.A. 56:4710 h]. Thus, the above hydrazine hydrochloride (34.0 g) was dissolved in 25% aqueous HOAc (1.4 L) at 80° C. Propionaldehyde diethyl acetal (22.1 ml) was then added and the reaction mixture stirred for 0.75 hour. Upon cooling to room temperature, ether was added to the reaction mixture and the layers were separated. The aqueous phase was extracted with ether (2*). The combined organics were washed with 5% aqueous NaOH until the aqueous extract was basic to litmus. The organic phase was then washed with brine and dried (K2 CO3). Filtration and concentration afforded 29.0 g of 3-methyl-5-benzyloxyindole. 3-Methyl-5-(phenylmethoxy)-1H-indol-1-amine was prepared using the procedure of Somei, et al., [Tetrahedron Lett. No. 5, pp. 461-462, 1974]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
2.1 g (50%) | With trifluoroborane diethyl ether In tetrahydrofuran; ethyl acetate | 16 3a,4,5,10b-Tetrahydro-2-ethyl-3a,6-ethano-1,3-dioxolo[4,5-d][1]benzazepine hydrochloride EXAMPLE 16 3a,4,5,10b-Tetrahydro-2-ethyl-3a,6-ethano-1,3-dioxolo[4,5-d][1]benzazepine hydrochloride A mixture of 3.08 g of 1,4-ethano-4,5-dihydroxy-2,3,4,5-tetrahydro-5H-1-benzazepine, 50 ml of anhydrous tetrahydrofuran, 7 ml of propionaldehyde diethylacetal and 5.2 ml of boron trifluoride etherate was stirred under nitrogen for 2 hrs at room temperature and for 1.5 hrs at 40° C. The reaction mixture was poured into excess ice-cold aqueous potassium carbonate solution and extracted twice with a mixture of ether and ethyl acetate. The extracts were washed with brine, dried and evaporated to give an oil. Purification by means of flash chromatography provided 2.1 g (57%) of product as an oil. The hydrochloride was prepared by dissolving the oil in anhydrous ether and adding dropwise ethereal hydrochloric acid. Filtration and drying yielded 2.1 g (50%) of product, mp 235°-237° C. (dec). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In dichloromethane | 13 EXAMPLE 13 EXAMPLE 13 1140 ml of a 3.40 molar aqueous solution of diammonium hydrogen phosphate (pH 8.3) was heated in a 2-liter autoclave to 230° C. and was then stirred at 1500 rpm. Into this solution, a mixture of 202.3 g of propionaldehydediethylacetal and 120.2 g of formaldehydedimethylacetal was continuously pumped within a 64 minute period (molar ratio of propionaldehydediethylacetal to formaldehydedimethylacetal=1 to 1). At the same time the reaction pressure varied between 32 and 46 bar. After completion of the addition of the educt mixture, the reaction mass continued to be stirred for 10 minutes at 230° C. and was then cooled to ambient temperature. An extraction was made 3 times with 100 ml of methylene chloride, and a gas chromatographic analysis was made of the combined methylene chloride extracts. The yield of 3,5-lutidine was 48.6 percent, based on the amount of propionaldehyde used. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
3.9% | With acetic anhydride In acetic acid chromy.; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
4.4% | With acetic anhydride In acetic acid chromy.; elem. anal.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With titanium tetrachloride; sodium hydrogencarbonate In dichloromethane B salt mixed with TiCl4 at -78°C, stirred at -78°C for 2 h, treated with aldehydes at -78°C, stirred at 0°C for 3 h,treated with aq.NaHCO3; extd.(AcOC2H5), chromy.(silica gel); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With sulfuric acid; acetic acid at 105 - 110℃; for 18h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With silver trifluoroacetate In benzene-d6 at 20℃; for 0.333333h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 1,1-diethoxypropane; di-tert-butyl 1-(6-methoxypyridin-3-yl)hydrazine-1,2-dicarboxylate With sulfuric acid In water for 1h; Reflux; Inert atmosphere; Stage #2: With sodium carbonate In water Saturated solution; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Stage #1: 1,1-diethoxypropane; di-tert-butyl 1-(2-methoxypyridin-3-yl)hydrazine-1,2-dicarboxylate With sulfuric acid In water for 1h; Reflux; Inert atmosphere; Stage #2: With sodium carbonate In water Saturated solution; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
41% | Stage #1: 1,1-diethoxypropane; di-tert-butyl 1-(2-methoxypyridin-3-yl)hydrazine-1,2-dicarboxylate With sulfuric acid In water for 1h; Reflux; Inert atmosphere; Stage #2: With sodium carbonate In water Saturated solution; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With copper(II) choride dihydrate In dimethyl sulfoxide at 100℃; for 6h; | 4.2 General procedure for the synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones General procedure: A mixture of 1-amino-1H-pyrrole-2-amides (0.3 mmol), CuCl2·2H2O 0.3 mmol) and aldehydes or acetals (0.3 mmol) in 5 mL of DMSO was heated at indicated temperature in air until completion. After cooling, the reaction solution was poured into 20 mL of water. The solid was precipitated, filtered to give the crude product, which was purified by column chromatography on silica gel, with CH2Cl2/MeOH as eluent to give the pure product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86 % ee | Stage #1: 1,1-diethoxypropane; dibenzyl azodicarboxylate With chloroacetic acid; trifluoroacetic acid; 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole In dichloromethane; water at 4℃; for 4h; Stage #2: With sodium tetrahydroborate In ethanol at 0℃; for 0.25h; Overall yield = 93%; | General procedure 1 (Compounds 1-4) General procedure: Dibenzyl azobicarboxylate (DBAD, 0.5 mmol, 2 equiv (1 mmol, 4 equivfor 4)) was added to a mixture ofacetal (0.25 mmol, 1 equiv), tetrazole catalyst (0.05 mmol, 20 mol%) monochloroaceticacid (MCA, 1.3 mmol, 5.2 equiv (2.6 mmol, 10.4 equiv for 4)), trifluoroacetic acid (TFA, 0.025 mmol, 0.1 equiv) and water(1.25 mmol, 5 equiv) in DCM (0.5 ml). The reaction mixture was kept at 4 0Cuntil complete consumption of the acetal was observed by TLC. On reactioncompletion, the reaction mixture was quenched with water (10 ml) and extractedwith DCM (3 x 10 ml) and the organic extracts were washed with saturated NaHCO3(10 ml) and brine (10 ml). The organic layers were then dried with MgSO4and the solvent was evaporated in vacuo.To the resultant residue was added EtOH (3 ml) and NaBH4 (0.5 mmol,2 equiv) at 0 0C and the mixture was allowed to warm up over 15minutes. The reaction was then quenched with saturated NH4Cl (10ml), extracted with DCM (3 x 10 ml) and the organic extracts were washed with brine(10 ml). The organic layer was then dried with MgSO4 and the solventwas evaporated in vacuo. The cruderesidue was then purified by flash column chromatography (ethyl acetate /petroleum ether) to give the desired product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With copper(l) chloride In cyclohexane at 45 - 65℃; for 12h; | 3 Example 3: Ethanol was added to the reaction vessel (3) 1.5mol, cuprous chloride 0.62mol, cyclohexane 500ml, 1- bromo-propylamine solution (2) 2.6mol, controlling the stirring speed 140rpm, temperature of the solution raised to 65 , reflux 5h , reducing the solution temperature to 45 , 7H reaction was continued, the temperature of the solution is reduced to 8 , allowed to stand 15H, layers were separated and the oil layer was separated, washed with a mass fraction of 70% acetamide, aqueous layers were combined, then the mass fraction of succinonitrile was washed with 60%, mass fraction of 45% triethylene glycol washed, dehydrated over phosphorus pentoxide, at 1.5kPa vacuum distillation, collecting the fraction 100--108 , the mass fraction of 85% N- dimethylformamide recrystallized to give crystals of 1,1-diethoxy propane 180.18g, yield 91%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | at 0 - 50℃; for 2.5h; | 1.2 2) Synthesis of 1,1,3,5-tetraethoxyheptane Take 1000ml three-necked flask,Add propionaldehyde diethyl acetal 340g,Then control the temperature 0 ~ 50 dropping vinyl ethyl ether 370g,Dropwise. The reaction was continued for 2.5 hoursCrude 730g, content of 85%Crude product obtained after rectification 1,1,3,5-tetraethoxyheptane 150g,Content of 92% to 95%, yield 73% to 75%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99 %Chromat. | With borane-ammonia complex; cobalt(II)(2,6-bis(morpholinomethyl)pyridine)bromide In methanol at 80℃; for 14h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With trifluorormethanesulfonic acid; tetrabutylammomium bromide In chloroform at 0℃; for 18h; Molecular sieve; Inert atmosphere; Sealed tube; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.6% | With palladium 10% on activated carbon; hydrogen In n-heptane at 100℃; | 1; 2 Example 1 - Selective acetal formation from orthoesters A solution of 1 ,1 , 1 -triethoxypropane [1] (17.6 g, 100 mmol) in heptane (200 mL) was passed over a bed of palladium on charcoal catalyst (10 wt.% loading of palladium) (0.880 mL) at a flow rate of 1 mL/ min (LHSV of 68 h"1), pressure of 90 barg and over a range of temperatures up to 125 °C (20, 50, 75, 100, and 125 °C). The reactions took place in the liquid phase. Products of each of the reactions were analysed by gas chromatography (GC) and results are provided in Table 2 below. The yield of the acetal [2] (1,1-diethoxypropane) from the orthopropionate [1] (1,1,1- triethoxypropane) was significant over the temperatures tested in Experiments A to E (20 °C up to 125 °C), with the greatest yield observed at a temperature of 100 °C (Experiment D). Very little conversion to the ether [4] (1-ethoxypropane) was observed over this temperature range. Comparative yields for the ether [4] and the acetal [2] are provided in Table 3 below which demonstrate that it is possible to control the extent of dealcoholation of the orthoester so as to favour formation of the acetal over the ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 63% 2: 36.9% | With palladium 10% on activated carbon; hydrogen In n-heptane at 150℃; | 2; 3 General procedure: A solution of 1 ,1 , 1 -triethoxypropane [1] (17.6 g, 100 mmol) in heptane (200 mL) was passed over a bed of palladium on charcoal catalyst (10 wt.% loading of palladium) (0.880 mL) at a flow rate of 1 mL/ min (LHSV of 68 h"1), pressure of 90 barg and over a range of temperatures up to 125 °C (20, 50, 75, 100, and 125 °C). The reactions took place in the liquid phase. Products of each of the reactions were analysed by gas chromatography (GC) and results are provided in Table 2 below. The yield of the acetal [2] (1,1-diethoxypropane) from the orthopropionate [1] (1,1,1- triethoxypropane) was significant over the temperatures tested in Experiments A to E (20 °C up to 125 °C), with the greatest yield observed at a temperature of 100 °C (Experiment D). Very little conversion to the ether [4] (1-ethoxypropane) was observed over this temperature range. Comparative yields for the ether [4] and the acetal [2] are provided in Table 3 below which demonstrate that it is possible to control the extent of dealcoholation of the orthoester so as to favour formation of the acetal over the ether. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic acid In ethanol at 15℃; for 2h; Large scale; | 1.1; 2.1; 3.1; 4.1 Add 2kg 9-deoxy-8a-aza-8a-high erythromycin A and 8.5L ethanol to the reaction kettle,Under stirring, add 165g of acetic acid and 4kg of propionaldehyde diethyl acetal successively,Stir at 15°C for 2 hours,Then 0.50 kg of sodium cyanoborohydride was added to it,React at 15°C for 20 hours,Get the reaction solution; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73.8% | With copper(l) iodide In acetonitrile at 30℃; for 12h; | 1 Synthesis of 1-(3-(3-bromo-2-methylphenoxy)propyl)-4-(diethoxymethyl)-1H-1,2,3-triazole (VII-1 ) Put VI-1 (4.50g, 16.7mmol),Propionaldehyde diethyl acetal (2.88mL, 20.1mmol),Cuprous iodide (0.16g, 0.84mmol)And acetonitrile (30mL) were added to the eggplant-shaped flask successively, and reacted at 30°C for 12 hours.TLC (petroleum ether: ethyl acetate = 8:1) monitors the complete reaction of the raw materials,Stop heating and cool to room temperature.Suction filtration to remove insoluble materials, slowly pour the filtrate into water (50mL),Extract with ethyl acetate (30mL×3), combine the organic phases,Wash with water (30mL×2) and saturated NaCl solution (30mL×2) respectively,After drying with anhydrous sodium sulfate, filtering with suction, removing the solvent under reduced pressure and performing column chromatography to obtain 4.89 g of a colorless transparent liquid with a yield of 73.8%.Since the product is a mixture, it will be purified together in the next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47% | With chloro[1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]copper(I); 3,5-difluoro-2,4,6-tris(N-phenylanilino)benzonitrile; N-benzyl-N,N,N-triethylammonium chloride; triphenylphosphine In dichloromethane at -20 - 20℃; for 20h; Inert atmosphere; Sealed tube; Irradiation; |
Tags: 4744-08-5 synthesis path| 4744-08-5 SDS| 4744-08-5 COA| 4744-08-5 purity| 4744-08-5 application| 4744-08-5 NMR| 4744-08-5 COA| 4744-08-5 structure
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H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
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