* 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.
With sodium carbonate In water at 20℃; for 5 h; Green chemistry
General procedure: To a solution of activated alkene(0.5 mmol) in alcohol (2.0 mmol) was added Na2CO3 (0.2 mL, 0.05 M aq.), and the solution wasstirred until alkene was completely consumed (monitored by TLC) or an appropriate time andextracted with ethyl acetate (3 ×5 mL). The combined organic layers washed with brine (10 mL),dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by silicagel column chromatography to give the β-alkoxycarbonyl compound.
100 %Chromat.
at 50℃; for 1 h;
General procedure: The cyanoethylation reaction procedure was similar to that previously reported [3]. Typically, 80 mmol of acrylonitrile and 20 mL of alcohol (methanol or 2-propanol) were added to a three-necked 50-mL round-bottom flask equipped with a reflux condenser and a thermometer. The solution was magnetically stirred at 50 °C, and the freshly activated catalyst was rapidly added to the reactor in order to minimize exposure to atmospheric CO2. Once the reaction started, aliquots were periodically taken from the reaction mixture, filtered and analyzed on an HP-6890 GC equipped with a 60-m HP-5 (5percent-phenyl-methylpolysiloxane) capillary column. Conversion was calculated following the decrease in acrylonitrile concentration.
Reference：
[1] Inorganic Chemistry, 2010, vol. 49, # 13, p. 6203 - 6213
[2] Tetrahedron, 2011, vol. 67, # 14, p. 2562 - 2569
[3] Tetrahedron, 1981, vol. 37, # 16, p. 2905 - 2908
[4] Tetrahedron Letters, 2014, vol. 55, # 49, p. 6718 - 6720
[5] Journal of the American Chemical Society, 2003, vol. 125, # 29, p. 8696 - 8697
[6] Chemical Communications, 2005, # 2, p. 227 - 229
[7] Journal of the American Chemical Society, 1945, vol. 67, p. 1505
[8] Journal of the Chemical Society, 1945, p. 536
[9] Journal of the American Chemical Society, 1945, vol. 67, p. 1505
[10] Journal of the Chemical Society, 1945, p. 536
[11] Journal of the American Chemical Society, 1945, vol. 67, p. 1505
[12] Journal of the Chemical Society, 1945, p. 536
[13] Industrial and Engineering Chemistry, 1952, vol. 44, p. 2871
[14] Bulletin of the Chemical Society of Japan, 1969, vol. 42, p. 2596 - 2599
[15] Journal of the Chemical Society [Section] C: Organic, 1968, p. 1479 - 1483
[16] Canadian Journal of Chemistry, 1969, vol. 47, p. 1965 - 1979
[17] Zeitschrift fur Chemie, 1980, vol. 20, # 10, p. 380 - 380
[18] Chemical Communications, 1998, # 10, p. 1091 - 1092
[19] Journal of Catalysis, 2011, vol. 279, # 1, p. 196 - 204
[20] Catalysis Letters, 2014, vol. 144, # 1, p. 117 - 122
[21] Chinese Journal of Catalysis, 2014, vol. 35, # 2, p. 264 - 269
[22] Catalysis Communications, 2011, vol. 12, # 8, p. 712 - 716
[23] Australian Journal of Chemistry, 2015, vol. 68, # 6, p. 981 - 986
[24] Synthetic Communications, 2016, vol. 46, # 7, p. 581 - 585
[25] Journal of the American Chemical Society, 2017, vol. 139, # 34, p. 11857 - 11867
[26] Patent: CN106883136, 2017, A, . Location in patent: Paragraph 0039; 0042-0044
[27] Patent: CN106966923, 2017, A, . Location in patent: Paragraph 0037; 0041; 0042
3
[ 67-56-1 ]
[ 107-13-1 ]
[ 151-18-8 ]
[ 110-67-8 ]
[ 107-12-0 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2004, vol. 346, # 12, p. 1487 - 1493
With hydrogen; at 60 - 98℃; under 1500.15 - 22502.3 Torr; for 6h;
Under the vacuum nickel catalyst of Raney nickel, silver nitrate suction also reduction, then absorbing 3 - methoxypropionitrile, shut off the vacuum valve and the feed valve, the opening degree of the air valve, the air in the [...] nitrogen, at least three times, each 0.2 mpa and slow exhaust emptying, to stir the permutation, open jacket cooling water, the opening degree of the valve ammonia, ammonia liquid, stop stirring and open valve penetrable, hydrogen replacement three times in order to exclude residual nitrogen, each 0.2 mpa and slow exhaust emptying, to close the valve and then started to stirring and heating up to 60 C start access hydrogen, to maintain the pressure in the 3 mpa, reduction kettle jacket and an inner tube through cooling water, kettle reaction temperature is controlled at 98 C.When the hydrogen pressure is not decreased, shows that the reaction has been to a terminal point, stationary and a half hours, cooling to normal temperature, pressure relief, then through nitrogen replacement three times, after the settlement in the barrel into the high nitrogen deposition 6 hours, a small amount of catalyst and the lower impurity collection, the upper fluid distillation.Reduction of the [...] still trapped in the bottom of the Raney nickel catalyst, methanol be retained as under the supplement.The settling of the barrel into the reduced pressure distilling the supernatant, closing the vent valve, the vacuum valve is opened, to maintain the vacuum degree less than -0.09 mpa, when the ruled in 80 C before the start of the liquid fraction collected, when the [...] reach 60 C collected at the time of the main fraction, in the collection [...] control the liquid temperature to 90 C, until the collection is completed, by chromatographic detection, content is greater than 99% is defective, yield 95%.Methanol, acrylonitrile in a molar ratio of 1: 1.03; 3 - methoxypropionitrile, ammonia water molar ratio of 1: 1.15; Raney nickel catalyst amount is 3 - methoxypropionitrile quality of 0.006%.
To a solution of 3-methoxypropionitrile in step S1, an acidic catalyst and water were added, heated to carryout hydrolysis reaction to obtain 3-methoxypropionic acid;
With water; at 95℃;Acidic conditions;
3-methoxy propionitrile in step S1 was added acidic catalyst and water, the hydrolysis reaction was filtered to 3-methoxy propionic acid;
With N-hydroxyphthalimide; oxygen;cobalt(II) acetate; In acetic acid; at 130 - 190℃; under 6750.68 Torr; for 3 - 7h;
methyl cyanoacetate9 bar of O2 were injected into a solution of 3.0 g (0.035 mol) of 3-methoxypropionitrile (Fluka), 0.5 g (3.0 mmol) of NHPI (N-hydroxy-phthalimide) and 57 mg (0.23mmol) of Co(CH3COO)2.4H2O in 50 ml of acetic acid in a pressure autoclave. The mixture was subsequently stirred at 150 C. for 5 h.
Example 2 Synthesis of 1,3-dimethoxypropanimine(compound 2) Cold 4M hydrogen chloride in dioxane (294 ml, 1.176 mol) is added to a stirred and cooled (0 C.) solution of 3-methoxypropionitrile (25 g, 0.294 mol) in anhydrous methanol (36.4 ml, 0.9 mol) and anhydrous ether (100 ml.) The resulting reaction mixture is stirred at 0 C. for an additional hour and then it is placed in a refrigerator (0-5 C.) for 48 hours (during this time a small amount of white crystalline material precipitated). The reaction mixture is removed from the refrigerator and warmed to approximately 40 C. using a warm water bath. Nitrogen gas is then bubbled through the warm reaction mixture to remove excess hydrogen chloride. The volume of the solvent is reduced in vacuo, and anhydrous ether is added to effect precipitation. The precipitate is collected by filtration, washed with ether and dried under vacuum to afford 38.7 g (86%) of the crystalline imidate hydrochloride salt (2) as a white solid. 1H NMR (CDCl3): delta 12.72(br s, 1H), 11.80(br s, 1H), 4.30(s, 3H), 3.80(t, J=5.65 Hz, 2H), 3.25(s, 3H), 2.95 (t, J=5.54 Hz, 2H). 13C NMR (CDCl3): delta 178.9, 67.7, 61.3, 59.2, 34.0.
With acetamide;palladium dichloride; In tert-butyl isocyanide;
Example 19 A solution of 3-methoxypropionitrile (182 muL, 2.0 mmol), acetamide (496 mg, 10.1 mmol), and PdCl2 (17.7 mg, 0.10 mmol) in 10 mL of trimethylacetonitrile was heated to reflux for 48 hours. GC-MS of the product solution showed that 3-methoxypropionamide and trimethylacetamide formed. Acetonitrile was also formed.
11.7 mL of trimethyl aluminum (23.4 mmol, 2.0M in toluene) was dropwise added at room temperature to 20 mL (23.4 mmol) of toluene containing 1.26 g of ammonium chloride. After stirring for 1.5 hours, 2 g (23.4 mmol) of 3-methoxypropanenitrile was added thereto, followed by heating at 85C for 9 hours. After a reaction, the solution was cooled, then 100 mL of chloroform containing 200 g of silicagel was added thereto, followed by filtering. After washing with 100 mL of methanol and then distillation, 2.35 g (23 mmol) of the title compound was obtained in a yield of 98%.[1307] NMR: 1H-NMR (CD3OD) delta 3.70 (2H, t, J = 7.0 Hz), 3.39 (3H, s), 2.73 (2H, t, J = 7.0 Hz)
ruthenium(II)dichloro-tris-triphenylphosphine[ No CAS ]
[ 110-67-8 ]
[ 75-87-6 ]
[ 107-13-1 ]
[ 16063-70-0 ]
Yield
Reaction Conditions
Operation in experiment
EXAMPLE 9 17.7 g of trichloroacetaldehyde, 5.3 g of acrylonitrile, 0.3 g of ruthenium(II)dichloro-tris-triphenylphosphine [T. A. Stephenson and G. Wilkinson, Inorg. Nucl. Chem., 28, 945 (1966)] and 30 ml of 3-methoxypropionitrile are heated for 2 hours at 170 C. in an enamel autoclave. After processing in a manner analogous to that described in Example 1, the yield is 10.5 g (58% of theory) of 2,3,5-trichloropyridine. 2,3,5-Trichloropyridine is obtained in likewise good yield by replacing in the above example the 3-methoxypropionitrile by butyronitrile.
4-(3,4-dimethoxyphenyl)-4-cyano-5-methylcapronitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium methylate; In N-methyl-acetamide; water;
(b) Preparation of 4-(3,4-dimethoxyphenyl)-4-cyano-5- methylcapronitrile 438.4 g (2 mol) of alpha-isopropyl-veratryl cyanide and 204.2 g (2.4 mol) of 3-methoxypropionitrile are dissolved in 400 ml of dimethylformamide, 36 ml of a 5.5 molar solution of sodium methylate are added, and the mixture is heated to 85 C. for 1/2 hour. After cooling, water is added to the reaction mixture and the reaction product separates by crystallisation. Recrystallized from methanol/water, the product melts at 97 C. Yield: 506 g=92.9% of theoretical.
α-(3,4-dimethoxy-benzal)-β-methoxy-propionitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
85%
In methanol; water;
EXAMPLE 1 A mixture of 200 g (1.20 mole) of 3,4-dimethoxy-benzaldehyde, 150 g (1.75 mole) of beta-methoxy-propinitrile, 260 ml of methanol and 10 g of a 55% methanolic potassium hydroxide solution is stirred at 60-62 C. for 8 hours, whereupon the reaction mixture is cooled to 30 C., and 170 g of a 55% methanolic potassium hydroxide solution are added dropwise. The reaction mixture is stirred for 5 hours and diluted with 1000 ml of water. The precipitated crystalline product is filtered, washed with methanol and water. Thus 280 g of alpha-(3,4-dimethoxy-benzal)-beta-methoxy-propionitrile are obtained, yield 85%, mp.: 82-83 C.
β-(dimethoxymethyl)-3,5-dimethoxy-4-(1-hydroxypropyl)-hydrocinnamic acid nitrile[ No CAS ]
[ 110-67-8 ]
[ 50-01-1 ]
[ 55687-84-8 ]
[ 55687-82-6 ]
[ 55687-83-7 ]
Yield
Reaction Conditions
Operation in experiment
With sodium; In methanol; water; benzene;
EXAMPLE 24 Preparation of 4-[(2,4-diamino-5-pyrimidinyl)-methyl]-alpha-ethyl-2,6-dimethoxy-benzyl alcohol From 3.5 g. of beta-(dimethoxymethyl)-3,5-dimethoxy-4-(1-hydroxypropyl)-hydrocinnamic acid nitrile, 2.29 g. of guanidine hydrochloride, 0.56 g. of sodium and 35 ml. of methanol, there is obtained in an analogous manner to that described in Example 23, 4-[(2,4-diamino-5-pyrimidinyl)-methyl]-alpha-ethyl-2,6-dimethoxy-benzyl alcohol, having a m.p. of 235-238 from methanol. The starting material can be prepared as follows: In a solution comprising 0.18 g. of sodium metal in 50 ml. of absolute methanol there is dissolved 2.74 g. of beta-methoxypropionitrile and 4.8 g. of 4-(1-hydroxypropyl)-3,5-dimethoxy-benzaldehyde and heated at reflux for 48 hours. The mixture is evaporated and the residue is taken up in 50 ml. of benzene and 10 ml. of water. The aqeuous phase is washed with two portions of 20 ml. each of benzene. The combined benzene phases are dried and evaporated. The residue (the yellow oil) is used in this form. A sample obtained through preparative thin layer chromatography (silica gel ether as the elution solvent) yields alpha-(dimethoxymethyl)-3,5-dimethoxy-4-(1-hydroxypropyl)-hydrocinnamic acid nitrile as a colorless oil.
With potassium hydroxide; sodium methylate; In methanol; 2-(2-methoxyethoxy)ethyl alcohol; 2-methyl-propan-1-ol; water;
EXAMPLE 1 2,4-Diamino-5-(4-methoxy-benzyl)-pyrimidine A mixture of 27.2 g (0.2 mole) of 4-methoxy-benzaldehyde (Fluka 10440), 2.5 g of 3-methoxy-propionitrile, 70 ml of methanol and 3 g of potassium hydroxide is stirred at 60 C. for 8 hours, whereupon the reaction mixture is cooled, diluted with 500 ml of water and extracted twice with 100 ml of benzene each. The organic layer is dried and evaporated in vacuo. The residue is dissolved in 50 ml of diethylene glycol monomethyl ether, then 3 g of powdered sodium methylate are added, the mixture is heated to 75-77 C. and stirred at this temperature for 3 hours. To the mixture 80 ml of isobutanol, 53 g of guanidine hydrochloride and a 30% methanolic solution of 27 g of sodium methylate are added. The reaction mixture is heated to 92 C. whereby methanol is distilled off. The reaction mixture is heated at this temperature for 7 hours, then cooled, the precipitated crystals are filtered and recrystallized from aqueous ethanol. Thus 23.2 g of the desired compound are obtained, yield 57%. M.p.: 206-209 C. Analysis for the Formula C12 H14 N4 O: calculated: C%=62.59; H%=6.13; N%=24.33; found: C%=62.61; H%=5.96; N%=24.21.
3,5-dimethoxy-4-methyldioxymethylene-benzaldehyde[ No CAS ]
[ 110-67-8 ]
[ 113-00-8 ]
2,4-diamino-5-(3',5'-dimethoxy-4'-methyldioxymethyl-benzyl)-pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium methylate; sodium; In methanol; water;
EXAMPLE 2 Production of 2,4-diamino-5-(3'-5'-dimethoxy-4'-methyldioxymethyl-benzyl)-pyrimidine. 225 g of 3,5-dimethoxy-4-methyldioxymethylene-benzaldehyde and 125 g of beta-methoxypropionitrile were stirred into a paste and mixed with 700 ml of sodium methylate (containing 70g of sodium) at 5 to 10 C. After stirring overnight, 59 g was added of guanidine base dissolved in 500 ml of methanol, and the whole was heated for 20 hours under reflux conditions. The precipitated product was drawn off and the reactive solution was concentrated further. The total precipitated productwas dissolved in water and filtered through activated charcoal. The melting point of the precipitated product was 185 C.
EXAMPLE 3 Preparation of 2,4-diamino-5-(4-fluoro-3,5-dimethoxybenzyl)-pyrimidine 1.6 G. of beta-methoxypropionitrile and 1.65 g. of 4-fluoro-3,5-dimethoxybenzaldehyde were dissolved in a solution of 0.11 g. of sodium metal in 15 ml. of absolute methanol and heated at reflux for 3 hours. The mixture was evaporated and the residue taken up in 50 ml. of benzene and 10 ml. of water. The aqueous phase was washed twice with 20 ml. of benzene each time. The combined benzene extracts were dried and evaporated. The resulting 4-fluoro-3,5-dimethoxy-alpha-(methoxymethylene)-hydrocinnamic acid nitrile was employed in the subsequent reaction.
3,5-dimethoxy-4-chloro-α-(methoxymethyl)-cinnamic acid nitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium; In methanol;
A mixture of a methanolic sodium methylate solution (prepared by dissolving 1.15 g. of sodium in 100 ml. of methanol), 17 g. of beta-methoxypropionitrile and 20 g. of 4-chloro-3,5-dimethoxybenzaldehyde was heated to reflux for 3.5 hours. On cooling, 3,5-dimethoxy-4-chloro-alpha -(methoxymethyl)-cinnamic acid nitrile crystallized, melting point 112-113 C.
3-ethoxy-3,4-methylenedioxy-α-methoxymethylcinnamonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With sodium; In methanol; water;
EXAMPLE 3 Preparation of 3-ethoxy-3,4-methylenedioxy-alpha-methoxymethylcinnamonitrile To a solution containing 2.16 g. of sodium in 100 ml. methanol, there were added 32 g. of beta-methoxypropionitrile and 36.5 g. of 3-ethoxy-4,5-methylenedioxy benzaldehyde. Thereafter, the mixture was refluxed for 6.5 hours. 300 ml. of water were added and the 3-ethoxy-3,4-methylenedioxy-alpha-methoxymethylcinnamonitrile was extracted with methylenechloride. Upon evaporation of the solvent and vacuum distillation, the 3-ethoxy-3,4-methylenedioxy-alpha-methoxymethyl-cinnaminonitrile had a b.p. of 175/0.3 mmHg and m.p. of 64-65. Analysis - C14 H15 NO4 Calc'd: C, 64.36; H, 5.79; N, 5.36. Found: C, 64.57; H, 5.83; N, 5.28.
2.45 G. of beta-methoxy-propionitrile and 5 g. of alpha,3,5-trimethoxy-tolualdehyde were dissolved in a solution of 0.25 g. of sodium metal in 20 ml. of absolute methanol and the resulting mixture was boiled at reflux for 48 hours. No aldehyde could be detected after this time. After evaporation of the solvent, the residue was taken up in 50 ml. of benzene and 15 ml. of water. The benzene phase was separated, washed several times with water, dried over magnesium sulfate and evaporated, whereby there was obtained a yellowish oil which was used in the process described in the first paragraph of this Example with no further working-up. An analytical sample was purified by chromatography on silica gel using ether as the eluant, whereby there was obtained alpha-(dimethoxymethyl)-3,5-dimethoxy-4-(methoxymethyl)-hydrocinnamic acid nitrile as a colorless crystalline substance, having a m.p. of about 30.
With sodium methylate; In methanol; water; benzene;
A solution of 1 g. of 4-isopropenyl-3,5-dimethoxybenzaldehyde, 0.375 g. of beta-methoxy-propionitrile and 0.1 g. of sodium methylate in 5 ml. of methanol was heated under reflux for 24 hours. The solvent was removed, the residue was dissolved in 10 ml. of benzene and 5 ml. of water and the benzene phase was separated, repeatedly washed with water, dried and concentrated. There was obtained 0.92 g. of 4-isopropenyl-3,5-dimethoxy-alpha-(methoxymethylene)-dihydrocinnamic acid nitrile which melted at about 40 C. after purification by chromatography on silica gel with ether.
cis-amminedichloro(3-methoxypropionitrile)platinum(II)[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
29%
In water; for 24h;Heating / reflux;
To a solution of K[PtNH3Cl3] (150 mg) in 4 mL of deionized water was added 0.3 mL of 3-methoxypropionitrile. The resulting mixture was heated and stirred for 24 hours. The pale yellow precipitate was filtered, washed with deionized water and ethyl ether, and dried under high vacuum to give a crude product. Recrystallization from tetrahydrofuran and acetone afforded a pure product (pale yellow solid, 38 mg; 29%). 1H NMR in acetone-d6: delta: 3.25 (t, 2H), 3.68 (t, 2H), 3.94 (br, 3H). 195Pt NMR 6-2248 ppm. Predicted HRMS for C4H10Cl2N2OPtNa+: 389.97100 amu found: 389.97047 amu.
To a solution of potassium tetrachloroplatinate (450 mg, 1.2 mmol) in deionized water (15 mL), 3-methoxy-propionitrile (950 mg, 11.2 mmol) was added and stirred at room temperature for 3 days. The reaction mixture was extracted with diethyl ether (3-times with 20 mL) and was filtered on a Buckner flask. Solids were washed sequentially with water and ether, and finally dried under vacuum to yield the designed product.1H NMR (DMF-d7, 300 MHz): delta 3.71(t, 4H, J=5.7 Hz), 3.54(t, 4H, J=5.7 Hz), 3.37(s, 6H). 195Pt (DMF-d7, 64.5 MHz): delta -2336.8
With hydroxylamine; In ethanol; water; at 90℃; for 16h;
Preparation 23: N-Hydroxy-3-methoxypropionamidineNH2<strong>[110-67-8]3-Methoxypropionitrile</strong> (11.75 mmol) was dissolved in ethanol (7 mL) and hydroxylamine (50% aqueous solution, 47 mmol) was added. The mixture was stirred at 90 C for 16 h. The mixture was concentrated under vacuum and remaining water azeotroped with toluene to afford the title compound: deltaH (400 MHz, CDCl3) 2.39 (t, /=5.66 Hz, 2H) 3.36 (s, 3H) 3.59 (t, /=5.66 Hz, 2H).
With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 20℃; for 16h;
A solution of the appropriate nitrile (1.0 eq.) in a mixture of ethanol (1.9 ml/mmol) and water (0.5 ml/mmol) is admixed at RT with hydroxylammonium chloride (1.08 eq.) and sodium hydroxide (1.12 eq.). The reaction mixture is stirred at room temperature for 16 h. For workup, the reaction mixture is concentrated under reduced pressure, admixed with dichloromethane and filtered. The filtrate is concentrated under reduced pressure and the residue is converted without further purification. According to General Method 6A, 20.0 g (235.0 mmol) of 3-methoxypropionitrile were converted.Yield: 18.1 g (49% of theory, 74% purity).HPLC (Method 1A): Rt=0.35 min; MS (ESIpos): m/z=119 [M+H]+.
Example 104 (S)-2-[4-(2-Chloro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid [3-(2-methoxy-ethyl)-[1,2,4]thiadiazol-5-yl]-amide To a stirred suspension of aluminum chloride (4.81 g, 0.090 mol) in toluene (33.5 ml) at 0 C. under argon was slowly added a solution of 2M trimethylaluminum in toluene (42 mL, 0.084 mol) maintaining a temperature below 10 C. The resulting mixture was allowed to stir at room temperature for 2 h before a solution of 3-methoxypropionitrile (4.26 g, 0.050 mol) in toluene (16.5 ml) was added. The resulting mixture was warmed to 80 C. and allowed to stir for 18.5 h. the reaction mixture was cooled to room temperature and then slowly poured on to a cooled suspension of silica gel (50 g) in dichloromethane (100 mL). the resulting mixture was stirred for 15 min, filtered and the silica gel pad washed well with methanol. The filtrate was evaporated and the residue was redissolved in a solution of dichloromethane/methanol, filtered and evaporated which afforded a solid. The solid was suspended in a 3N hydrogen chloride solution in methanol (20 mL) and stirred vigorously while diethyl ether (500 mL) was added dropwise. The resulting mixture was stirred at room temperature for 1 h decanted and dried under vacuum which afforded 3-methoxy-propionamidine hydrochloride (4.8 g, 69%) as a white solid.
With hydroxylamine hydrochloride; sodium hydrogencarbonate; In methanol; for 16h;Reflux;
Preparation Example 4-29-1N-Hydroxy-3-methoxypropionamidine Hydrochloric acid salt of hydroxylamine (171.5 mg, 2.47 mmol) was dissolved in methanol 4 mL, sodium hydrogen carbonate (207.3 mg, 2.47 mmol) was added thereto and then, stirred for 20 minutes at room temperature. 3-methoxypropionitrile (200 mg, 2.35 mmol) was added thereto, heated, and stirred for 16 hours with reflux and then, cooled to room temperature. Formed salt was filtrated and removed. After distillation of the filtrate under reduced pressure, the title compound (164.3 mg, 59%) was obtained by column-chromatography using 10:1 mixture of dichloromethane and methanol.Mass: M+H 119
With bis(cyclopentadienyl)titanium dichloride; methyloxirane; zinc; In tetrahydrofuran; for 18.5h;Inert atmosphere; Reflux;
General procedure: To a mixture of Cp2TiCl2 (1.2 mmol) and activated Zn powder (48 mmol), under a nitrogen atmosphere, is added deoxygenated THF (30 mL). To this mixture, nitrile (12 mmol, 0.4 mol mL-1); diethyl phosphite (48 mmol); and propylene oxide (24 mmol) are successively added. The reaction mixture is heated to reflux, with continuous stirring, until no further formation of products can be observed by 31P-NMR monitoring. Depending on the nature of the bisphosphonate different protocols of purification were used and are listed below. Purification protocol by acid/base extraction: The reaction mixture was filtered through filter paper and concentrated in vacuo. The residue was dissolved in CH2Cl2 or AcOEt (30 mL) and aqueous HCl (1 M) was added. The organic layer was removed and the aqueous layer was washed once more CH2Cl2 or AcOEt (30 mL). The aqueous phase was basified to pH = XX with NaHCO3 (1 M) and was extracted three times with CH2Cl2 or AcOEt. The combined organic phases are dried over MgSO4 and concentrated in vacuo. Purification protocol by column chromatography: Purification by chromatography on silica gel using a gradient of solvents: CH2Cl2 to [CH2Cl2/EtOH, 9/1]. Purification protocol by oxidation of the residual diethyl phosphite and extraction: The reaction mixture is filtered through filter paper and concentrated in vacuo. The oil is redissolved in HCl (30 mL, 1 M). Hydrogen peroxide is added to the mixture (40 mL) and left to stir for 30 min. A color change from yellow, to orange, to red is observed. The mixture is basified using NaOH (25 mL, 4 M). The product is extracted with CH2Cl2 (3 × 150 mL). The combined organic phases were dried over MgSO4 and concentrated in vacuo.
With hydroxylamine; In ethanol; water; for 16h;Reflux;
To a solution of 3-methoxypropionitrile (1.07mL, 11.8mml) in EtOH (7mL) was added a solution of hydroxylamine (50% in water, 3. lmL, 51.2mmol) and the reaction was heated to reflux for 16 h. The solvent was removed in vacuo, azeotroping with toluene, to afford the intermediate product N-Hydroxy-3-methoxypropionamidine.
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