* 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 tetrahydroborate In dimethoxyethane, 1,2; ethanol at 50℃; for 7 h; Heating / reflux
302,6 g (8 mol) of sodium borohydride was added to 2 1 of 1,2-dimethoxyethane (monoglyme) with stirring, after which 704,8 g (4 mol) ethyl diethoxyacetate dissolved in 4 1 of ethanol was added dropwise within 4 hours so that the temperature was kept below 50 °C. The mixture was then heated to reflux for 3 hours. Then 2 1 of ethanol was distilled off, and 4 1 of water was added dropwise while the remaining ethanol and then the 1,2-dimethoxyethane was removed by distillation. During the water addition an abundant precipitate was formed which dissolved towards the end of the addition. The mixture was cooled on an icebath and 600 g of potassium carbonate was dissolved therein while stirring. The mixture was extracted with 2 1 of diethyl ether and dried with MgSO4. The diethyl ether was evaporated off and the crude product was distilled in vacuo at 75-76 °C (15 mm Hg). Yield = 475.8 g = 88.7 percent [] Elemental analysis: CalculatedC 53.7percentH 10.5percentFoundC 53.11percentH 10.57percentIR: 3441 cm-1; 2976 cm-1; 2931 cm-1 ; 2883 cm-1; 1445 cm-1 1374 cm-1; 1345 cm-1; 1235 cm-1; 1134 cm-1; 1073 cm-1 (Between KBr plates)
The stainless steel pressure vessel (40 cc, Swagelok) is filled in with the methanol (15.0 g: Sigma-Aldrich, 003e99.8percent) solution of the metal salt (metal ion supply source), and sucroses (0.450 g: Fluka, 003e99.0percent) and catalyst (0.150 g). The reactor is closed and it heats up under the mixing (700 rpm) with 160. In 160 reaction, it makes maintained for 16 hours and the container reaction rapidly is cooled in the cold water after this period as the dipping. Sample from the reaction container was filtered and it analyzed with the HPLC (the Agilent 1200, the Biorad Aminex HPX-87H column, 65, 0.05 M H2SO4, 0.6 ml min-1) and it was the art exhibition ring hexose and dihydroxy acetone (DHA), the methyllactate (ML) using the fixed quantity: and GC (the Agilent 7890 in which the Phenomenex Solgelwax column is comprehended) the glyceraldehyde (GLA), and methyl vinyl glycol rate (MVG, and the methyl 2- hydroxy -3- butenoate) and glycol aldehyde dimethylacetal (GADMA) the fixed quantity.
Reference：
[1] Patent: KR2016/45675, 2016, A, . Location in patent: Paragraph 0054; 0055; 0056; 0057; 0058
4
[ 2032-35-1 ]
[ 621-63-6 ]
Reference：
[1] Journal of the American Chemical Society, 1936, vol. 58, p. 531
[2] Annales de Chimie (Cachan, France), 1949, vol. <12>4, p. 828
[3] Chemische Berichte, 1872, vol. 5, p. 150
[4] Journal of the American Chemical Society, 1927, vol. 49, p. 2518
[5] Journal of the American Chemical Society, 1936, vol. 58, p. 531
[6] Journal of the American Chemical Society, 1955, vol. 77, p. 6391
5
[ 621-62-5 ]
[ 621-63-6 ]
Reference：
[1] Journal of the American Chemical Society, 1936, vol. 58, p. 531
[2] Annales de Chimie (Cachan, France), 1949, vol. <12>4, p. 828
[3] Hoppe-Seyler's Zeitschrift fuer Physiologische Chemie, 1903, vol. 38, p. 144
[4] Bulletin de la Societe Chimique de France, 1958, p. 610,615
[5] Journal of Organic Chemistry, 1977, vol. 42, p. 2900 - 2902
With sodium tetrahydroborate; In dimethoxyethane, 1,2; ethanol; at 50℃; for 7h;Heating / reflux;
302,6 g (8 mol) of sodium borohydride was added to 2 1 of 1,2-dimethoxyethane (monoglyme) with stirring, after which 704,8 g (4 mol) ethyl diethoxyacetate dissolved in 4 1 of ethanol was added dropwise within 4 hours so that the temperature was kept below 50 °C. The mixture was then heated to reflux for 3 hours. Then 2 1 of ethanol was distilled off, and 4 1 of water was added dropwise while the remaining ethanol and then the 1,2-dimethoxyethane was removed by distillation. During the water addition an abundant precipitate was formed which dissolved towards the end of the addition. The mixture was cooled on an icebath and 600 g of potassium carbonate was dissolved therein while stirring. The mixture was extracted with 2 1 of diethyl ether and dried with MgSO4. The diethyl ether was evaporated off and the crude product was distilled in vacuo at 75-76 °C (15 mm Hg). Yield = 475.8 g = 88.7 percent [] Elemental analysis: CalculatedC 53.7percentH 10.5percentFoundC 53.11percentH 10.57percentIR: 3441 cm-1; 2976 cm-1; 2931 cm-1 ; 2883 cm-1; 1445 cm-1 1374 cm-1; 1345 cm-1; 1235 cm-1; 1134 cm-1; 1073 cm-1 (Between KBr plates)
4-methoxy-benzoic acid 2,2-diethoxy-ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
100%
With dmap; triethylamine; In ethyl acetate; at 0 - 20℃; for 16h;
4-Methoxy-benzoic acid 2,2-diethoxy-ethyl ester (2b) To a well-stirred solution of 2,2-diethoxy or 2,2-dimethoxy-ethanol (1, 100 mmol), DMAP (61 mg, 0.5 mmol) and Et3N (16 ml, 11.64 g, 115 mmol) in EtOAc or tert-butylmethyl ether (50 ml) at 0° C. was slowly added the corresponding acid chloride (105 mmol). After stirring for 16 h at room temperature the reaction mixture was diluted with EtOAc (50 ml), and successively washed with: (c) NaHCO3 (2*100 ml), brine (2*100 ml), dried, filtered and evaporated to afford: 4-Methoxybenzoic acid 2,2-diethoxy-ethyl ester (2b, 100percent) as a syrup that was used in the next step without any further purification. GC (Rt=13.7 min, 99percent); 1H-NMR (CDCl3) delta: 7.98 (2H, d, J=9.0, ArH), 6.89 (2H, d, J=9.0, ArH), 4.79 (1H, t, J=5.6, (EtO)2CHCH2-), 4.28 (2H, d, J=5.6, (EtO)2CHCH2-), 3.82 (3H, s, CH3O-), 3.73 (2H, m, CH3CH2O-),3.59 (2H, m, CH3CH2O-),1.22 (6H, t, J=6.9, CH3CH2O-).
100%
With dmap; triethylamine; In tert-butyl methyl ether; at 0 - 20℃; for 16h;
4-Methoxy-benzoic acid 2,2-diethoxy-ethyl ester (2b) To a well-stirred solution of 2,2-diethoxy or 2,2-dimethoxy-ethanol (1, 100 mmol), DMAP (61 mg, 0.5 mmol) and Et3N (16 ml, 11.64 g, 115 mmol) in EtOAc or tert-butylmethyl ether (50 ml) at 0° C. was slowly added the corresponding acid chloride (105 mmol). After stirring for 16 h at room temperature the reaction mixture was diluted with EtOAc (50 ml), and successively washed with: (c) NaHCO3 (2*100 ml), brine (2*100 ml), dried, filtered and evaporated to afford: 4-Methoxybenzoic acid 2,2-diethoxy-ethyl ester (2b, 100percent) as a syrup that was used in the next step without any further purification. GC (Rt=13.7 min, 99percent); 1H-NMR (CDCl3) delta: 7.98 (2H, d, J=9.0, ArH), 6.89 (2H, d, J=9.0, ArH), 4.79 (1H, t, J=5.6, (EtO)2CHCH2-), 4.28 (2H, d, J=5.6, (EtO)2CHCH2-), 3.82 (3H, s, CH3O-), 3.73 (2H, m, CH3CH2O-),3.59 (2H, m, CH3CH2O-),1.22 (6H, t, J=6.9, CH3CH2O-).
2,2-diethoxyethyl (2S)-2-(acetyloxy)phenylacetate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With triethylamine; In dichloromethane;
(d) 2,2-Diethoxyethyl (2S)-2-(Acetyloxy)phenylacetate A 3-necked, 250 mL, round bottom flask equipped with a stir bar and a condenser is charged with 2,2-diethoxyethanol (10 g), dry methylene chloride (100 mL) and triethylamine (9 g). The mixture is cooled to 0-5° C. over a period of 1-2 hours. The flask is slowly charged with (2S)-2-(acetyloxy)phenylacetyl chloride (16.6 g) while maintaining IT<10° C. over a period of 0.5-1 hour. The reaction is stirred at 15-20° C. for 1-2 hours. The reaction mixture is filtered and the filter cake is washed with dichloromethane (10 mL). The organic layer is transferred to a separatory funnel and washed with deionized water (2*40 mL) followed by brine (1*30 mL). The organic layer is dried over anhydrous sodium sulfate and evaporated to give 21 g of 2,2-diethoxyethyl (2S)-2-(acetyloxy)phenylacetate as a syrup.
2,2-diethoxyethyl (S)-(+)-camphorsulfonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With dmap; triethylamine; In dichloromethane; water;
(b) 2,2-Diethoxyethyl (S)-(+)-Camphorsulfonate 2,2-Diethoxyethanol (3.82 g), Et3N (3.17 g), dichloromethane (40 mL) and DMAP (4 mg) are combined and the solution is cooled to 4° C. (S)-Camphorsulfonyl chloride (7.5 g) is added at a rate of 1 g /min. The ice-water bath is removed and the reaction is allowed to progress for about 1 hour at room temperature. About 40 mL of water is added slowly to quench the reaction, the phases are separated and the dichloromethane phase is washed with saturated sodium bicarbonate (20 mL) and water (20 mL). The solution is vacuum concentrated to produce 7.9 g of 2,2-diethoxyethyl (S)-(+)-camphorsulfonate.
9,10-difluoro-2-(hydroxymethyl)-3-methyl-7-oxo-2,3-dihydro7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In 1,4-dioxane;
EXAMPLE 3 Preparation of 9,10-difluoro-2-(hydroxymethyl)-3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4-benzoxadiazine-6-carboxylic acid A suspension of 6,7-difluoro-8-hydroxy-1-(methylamino)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid (50 mg) obtained in Reference example (i). glycolaldehyde diethylacetal (45 mul) and pyridinium p-toluenesufonate (7 mg) in dry dioxane (2 ml) was heated at 110° C. for 5 hours under nitrogen atmosphere. After the solvent was removed under reduced pressure, the crystalline residue was washed with water and methanol to give 52 mg of 9,10-difluoro-2-(hydroxymethyl)- 3-methyl-7-oxo-2,3-dihydro-7H-pyrido[3,2,1-ij]-1,3,4- benzoxadiazine-6-carboxylic acid, mp 254°-258° C. (dec.); MS m/z 312 (M+).
To a suspension of sodium hydride (3.0 g, 60percent dispersion in mineral oil, 125 [MMOL)] in xylenes under nitrogen was added 2, 2-diethoxy-ethanol (15.3 g, 114 [MMOL)] dropwise via canula. The reaction was heated to reflux for two hours, cooled to ambient temperature followed by addition of 2-bromo-1,1-diethoxy-ethane (25.6 mL, 170 [MMOL)] dropwise. The reaction was then heated at reflux overnight. The xylenes were distilled off under atmospheric pressure. The title compound was distilled off under vacuum (6 mm Hg) at [120°C] (12.0 grams, 42 percent yield)
33%
To a suspension of NaH (60percent dispersion in mineral oil, 3.8 g, 95.0 mmol) in xylene (100 mL) was added 2,2-diethoxyethanol (1 1.6 g, 86.4 mmol) under N2. The mixture heated at 1 10 °C for 2 hours, then cooled to room temperature and 2-bromo-1 ,1 -diethoxyethane (25.6 g, 130.0 mmol) added. The reaction was heated at 1 10 °C overnight, then cooled to room temperature and the organic layer washed with water, dried (Na2S04), filtered and concentrated. The residue obtained was purified by distillation to give the title compound (7 g, 33percent) as colorless oil.
With potassium iodide; In tetrahydrofuran; diethyl ether; water; mineral oil;
Stage I Hydroxyacetaldehyde diethylacetal (3.75 g) was added to sodium hydride (0.8 g, 80percent in mineral oil) in tetrahydrofuran (100 ml) under an atmosphere of nitrogen. The mixture was stirred and bromoacetaldehyde diethyl acetal (5.0 g) and potassium iodide (0.1 g) were added. The mixture was heated to reflux for 16 hours, water added and evaporated under reduced pressure. The residue was dissolved in diethyl ether, the organic phase washed with water, dried (MgSO4) and evaporated under reduced pressure to give bis(2,2-diethoxyethyl)ether, 3.43 g, as a yellow oil. 1 H NMR (CDCl3): delta 1.20(12H,t); 3.60(8H,d); 3.70(4H,q); 4.60(2H,t)ppm.
With caesium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;
2,2-Diethoxyethanol (1.6 g) and cesium carbonate (5.8 g) were added to DMF solution (10 mL) of 5-bromo-2-chloropyrimidine (1.15 g), and stirred at room temperature for 12 hours. After addition of water, the reaction liquid was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was purified on silica gel column chromatography (C-200; ethyl acetate : hexane =1:9 -1:4) to provide the title compound (1.63 g, 94percent).
With edetate disodium; In tetrahydrofuran; for 0.5h;
A mixture of benzyl acrylate (60.4 g, 372 mmol) and glycolaldehyde diethyl acetal (10.16 g, 74.5 mmol) in dry THF (70 mL) was stirred vigorously and Triton B (1.7 mL, 5 molpercent) was added. The RM became dark brown gradually over about 0.5 minutes during which an exotherm was noted. The reaction mixture was concentrated in vacuo and purified directly over silica-gel (330 g, Companion) eluting from 0-100percent EtOAc/cyclohexane to give the title compound as acolourless oil.Yield 9.7 g (44percent)1H NMR (400 MHz, CDCI3) 57.34-7.29 (m, 5H), 5.13 (s, 2H), 4.58 (t, J = 5.2Hz, 1H), 3.80, (t, J = 6.4 Hz, 2H), 3.67 (m, 2H), 3.54 (m, 2H), 3.46 (d, J = 5.2 Hz, 2H), 2.64 (t, J = 6.4 Hz, 2H), 1.20 (t, J = 7 Hz, 6H).
Intermediate Aldehyde 2 a + HOv NaH/DMF C H2SO4 O N 0 Hz0/Dioxane Zu H OH Synthesis of (pyridin-2-yloxy)-acetaldehyde : To a stirred suspension of sodium hydride (30 mmol) in DMF (6 mL) was added, dropwise, 2-hydroxyacetaldehyde diethylacetal (30 mmol) and the mixture was agitated for 0.5 hrs. A solution of 2-chloropyridine (10 mmol) in DMF (2 mL) was then added and the mixture was stirred at 80 °C for 24 hrs. The reaction was quenched with ice-cold water, extracted with ether (2 x 150 mL), the combined organic extracts were dried and concentrated to give the crude intermediate acetal which was hydrolyzed as follows.
To a stirred suspension of 58,8 g 60 percent (1.47 mol) sodium hydride in 600 ml anhydrous tetrahydrofuran, a solution of 94 g (0.7 mol) 2,2-diethoxy-ethanol in 160 ml tetrahydrofuran was added dropwise, so that the temperature was kept below 40 'C. After completion of the addition, the reaction mixture was stirred for further 30 minutes. Then 115 g (0.7 mol) ethyl 4-chloroacetoacetate in 500 ml anhydrous tetrahydrofuran was added dropwise within 3 hours, so that the temperature was kept between 10 °C and 40 °C, preferentially at about 20 'C. The mixture was stirred overnight at room temperature. Then 90 ml ethanol was added dropwise, and the mixture was poured into 900 g of ice after which pH was adjusted to 6 with hydrochloric acid. The organic phase was separated and dried over MgSO4. The tetrahydrofuran was evaporated off and the product was separated from the oily layer in a separation funnel. Then the product was dissolved in toluene and purified by filtration through a short column of silica. The toluene was evaporated off, leaving the product as a light yellow oil. The product was purified by distillation in vacuo. yield: 130.9 g = 71.4 percent bp. = 112-114 'C at 0.2 mm Hg[] Elemental analysis: CalculatedC 54.9percentH 8.5percentFoundC 54.48percentH 8.7percentIR: 2986 cm-1; 1726 cm-1; 1748 cm-1; 1119 cm-1; 1067 cm-1 (Between KBr plates) NMR: 250 MHz 1H-NMR (CDCl3) (delta ppm): 4.646 (t, H, CH); 4.286 (s, 2H, CH2); 4.224 (s, 2H, CH2); 3,708 (q, 2H, CH2); 3.568 (q, 2H, CH2); 3.556 (d, 2H, CH2) ; 1.30 (t, 3H, CH3); 1.21 (m, 6H, CH3).
In tetrahydrofuran; N,N-dimethyl acetamide;Cooling with ice; Inert atmosphere;
With cooling with ice, a tetrahydrofuran solution (2 ml) of 2,2-diethoxyethanol (668 mg, 4.98 mmol) was added to a mixed tetrahydrofuran (4 ml)/N,N-dimethylacetamide (2 ml) solution of 2-chloro-5-fluoropyrimidine (600 mg, 4.53 mmol), and stirred under a nitrogen atmosphere for 1 hour. Water was added to the reaction solution, and extracted with ethyl acetate. Next, the organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (Moritex, acetone:hexane = 1:25) to obtain 2-(2,2-diethoxyethoxy)-5-fluoropyrimidine (699 mg, yield: 67 percent) as a colorless oil, and 2-chloro-5-(2,2-diethoxyethoxy)pyrimidine (233 mg, 21 percent) as a colorless solid.
For large scale synthesis, 2,2-diethoxyethanol was added dropwise into a suspension of 60percent sodium hydride in 5 L of THF at 1-2° C. over 30 minutes and then stirred at 0-5° C. for 1.5 hours. A solution of 750 g of 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline in 2.25 L of THF was then added dropwise into the above suspension at 0-5° C. After the addition, the purple solution was stirred at room temperature for 2 days and 17 hours. HPLC analysis showed 4.1percent remaining of 2,3,5-trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline. 150 mL of water was added very slowly (gas generated) into the pre-cooled solution at 10° C. The solution was then concentrated to dryness. The resultant oil was then suspended in 5 L of heptanes and seeded with pure 3-(2,2-diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2-nitroaniline crystal and stirred for 30 minutes. After 1 hour of stirring, the precipitate was filtered and dried to yield 520 g (54.3percent) of product with 96.4percent purity. Further product was available in the mother liquor. 1H NMR (CDCl3, 400 MHz): delta 7.42 (dd, 1H), 7.34 (d, 1H), 6.87 (bs, 1H), 6.56-6.67 (m, 2H), 4.79 (t, 1H), 4.06 (d, 2H), 3.74-3.82 (m, 2H), 3.59-3.66 (m, 2H); 1.24 (t, 6H).
54.3%
For large scale synthesis, 2,2-diethoxyethanol was added dropwise into a suspension of 60percent> sodium hydride in 5 L of THF at 1-2°C over 30 minutes and then stirred at 0-5°C for 1.5 hours. A solution of 750 g of 2,3,5-trifluoro-N-(2-fluoro-4- iodophenyl)-6-nitroaniline in 2.25 L of THF was then added dropwise into the above suspension at 0-5°C. After the addition, the purple solution was stirred at room temperature for 2 days and 17 hours. HPLC analysis showed 4.1percent> remaining of 2,3,5- trifluoro-N-(2-fluoro-4-iodophenyl)-6-nitroaniline. 150 mL of water was added very slowly (gas generated) into the pre-cooled solution at 10°C. The solution was then concentrated to dryness. The resultant oil was then suspended in 5 L of heptanes and seeded with pure 3-(2,2-diethoxyethoxy)-5,6-difluoro-N-(2-fluoro-4-iodophenyl)-2- nitroaniline crystal and stirred for 30 minutes. After 1 hour of stirring, the precipitate was filtered and dried to yield 520 g (54.3percent>) of product with 96.4percent purity. Further product was available in the mother liquor. XH NMR (CDC13, 400 MHz): delta 7.42 (dd, 1H), 7.34 (d, 1H), 6.87 (bs, 1H), 6.56-6.67 (m, 2H), 4.79 (t, 1H), 4.06 (d, 2H), 3.74-3.82 (m, 2H), 3.59- 3.66 (m, 2H); 1.24(t, 6H).
47%
Preparation of Intermediate 3-(2,2-Diethoxyethoxy)-5,6-difluoro-N-(2-fl oro-4- iodovhenyl)-2-nitroaniline (l-29a):(l-29a)2,2-Diethoxy-ethanol (0.209g, 1.2135mmol) was added to a cooled suspension of NaH (0.034g, 1.456mmol) in THF (5mL) at 0°C and the resulting mixture was stirred for 30 minutes at 20-40°C. 2-Fluoro-4-iodo-phenyl-(2,3,5-trifluoro-6-nitro-phenyl)-amine (0.5g, 1.2135mmol) in THF (lOmL) was added slowly to the reaction mass at 0°C and stirring was continued for a further 15 minutes. The reaction mass was stirred overnight at room temperature. The reaction was monitored by TLC (20percent ethyl acetate in hexane). The reaction mass was concentrated under reduced pressure and the concentrate was extracted with ethyl acetate. The organic layer was washed with water, brine solution, dried over sodium sulphate and concentrated under reduced pressure to afford the crude compound. Purification by column chromatography on silica gel (15percent ethyl acetate in hexane) afforded 0.3g of the product (47percent yield). NMR (CDCl3j 300 MHz): 6 7.42 (d, 1 H), 7.35 (d, 1 H), 6.90 (bs, I H), 6.58-6.68 (m, 2H), 4.58 (t, 1 H), 4.15 (d, 2H), 3.51- 3.80 (m, 4H), 1.22 (t, 6H).
4-tert-butyl-N-[6-chloro-5-(2-methoxyphenoxy)-2-(2-pyrimidinyl)-4-pyrimidinyl]benzene sulfonamide potassium salt[ No CAS ]
[ 621-63-6 ]
[ 1250871-99-8 ]
Yield
Reaction Conditions
Operation in experiment
Example 8Preparation of 4-tert-Butyl-N-[6-(2,2-diethoxy-ethoxy)-5-(2-methoxyphenoxy)-[2,2']bipyrimidin-4-yl]-benzene sulphonamide (compound 4A) using NaH and DMF; 4-t-butyl-N-[6-chloro-5-(o-methoxyphenoxy)-4-pyrimidinyl]benzenesulfonamide, potassium salt (3.0 gm, 0.0053 mol) was dissolved in N,N-dimethyl formamide (10 ml) at 30° C. under stirring. Glycolaldehyde diethylacetal (2.13 gm; 0.01587 mol) was added, followed by sodium hydride (60percent dispersion in mineral oil) (1.35 gm, 0.03375 mol). The reaction mass was stirred for 30-40 minutes after the addition of sodium hydride at 45-50° C. and at 30° C. for 3 hrs. Water (60 ml) was added to the reaction mass and acidified with Conc. HCl (1.0 ml). The resulting solution was stirred for 30 minutes at 30° C. and extracted with 2.x.25 ml of Ethyl Acetate.Combined Ethyl Acetate layer was washed with water (40 ml), dried over anhydrous sodium sulphate and evaporated under vacuum at 55-60° C. to give the diacetal compound as an oil (Weight of oil=4.63 gm).MS of oil: 624.2 [M+H], 578.2, 550.2, 508.2, 336.0, 310.9, 202.3
2-(2,2-diethoxy-ethoxy)-3,5-dinitropyridine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
35%
Part I - Synthesis of 2-(2,2-diethoxy-ethoxy)-3,5-dinitropyridine [0244] 2,2'-Diethoxyethanol (0.27 g, 2.5 mmol) was dissolved in THF to form a solution. NaH (60percent in mineral oil, 0.13 g, 3.4 mmol) was added to the solution, and the resulting reaction mixture was stirred at room temperature for 30 minutes. Next, l-chloro-2,5- dinitropyridine (0.34 g, 1.7 mmol) was added, and the reaction mixture was heated to 50 °C for 90 minutes. Next, the reaction mixture was cooled to room temperature, diluted with EtOAc, and washed with water and brine. The resulting organic solution was concentrated and purified by column chromatography (EtOAc/hexanes) to provide 2-(2,2-diethoxy- ethoxy)-3,5-dinitropyridine. Yield 0.18 g (35percent). LCMS (ESI): calc. CnHi5N307 = 301; obs. low ionization.
With potassium carbonate; at 160℃; for 16h;Flow reactor;
The stainless steel pressure vessel (40 cc, Swagelok) is filled in with the methanol (15.0 g: Sigma-Aldrich, 003e99.8percent) solution of the metal salt (metal ion supply source), and sucroses (0.450 g: Fluka, 003e99.0percent) and catalyst (0.150 g). The reactor is closed and it heats up under the mixing (700 rpm) with 160. In 160 reaction, it makes maintained for 16 hours and the container reaction rapidly is cooled in the cold water after this period as the dipping. Sample from the reaction container was filtered and it analyzed with the HPLC (the Agilent 1200, the Biorad Aminex HPX-87H column, 65, 0.05 M H2SO4, 0.6 ml min-1) and it was the art exhibition ring hexose and dihydroxy acetone (DHA), the methyllactate (ML) using the fixed quantity: and GC (the Agilent 7890 in which the Phenomenex Solgelwax column is comprehended) the glyceraldehyde (GLA), and methyl vinyl glycol rate (MVG, and the methyl 2- hydroxy -3- butenoate) and glycol aldehyde dimethylacetal (GADMA) the fixed quantity.
Trifluoro-methanesulfonic acid 2,2-diethoxy-ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With pyridine; In dichloromethane;
Scheme 6-3: In Step 1 the appropriately substituted and protected aniline is converted as known in the art to a sulfonamide. In Step 2 the appropriately substituted alcohol is converted as known in the art to a triflouro sulfonamide. In Step 3 the previously prepared reagents are subjected to sodium hydride to afford their adduct. In Step 4 the appropriately substituted ketal is subjected to a strong lewis acid to afford deprotection and subsequent cyclization to a biaryl species. In Step 5 the appropriately substituted sulfonamide is deprotected in the presence of base to afford a free amine. In an alternative embodiment this synthetic protocol can be applied to other aniline isomers to afford substituents on alternative positions.
With pyridine; In dichloromethane;Inert atmosphere;
In Step 1 the appropriately substituted and protected aniline is converted as known in the art to a sulfonamide. In Step 2 the appropriately substituted alcohol is converted as known in the art to a triflouro sulfonamide. In Step 3 the previously prepared reagents are subjected to sodium hydride to afford their adduct. In Step 4 the appropriately substituted ketal is subjected to a strong lewis acid to afford deprotection and subsequent cyclization to a biaryl species. In Step 5 the appropriately substituted sulfonamide is deprotected in the presence of base to afford a free amine. In an alternative embodiment this synthetic protocol can be applied to other aniline isomers to afford substituents on alternative positions.
With pyridine; In dichloromethane;Inert atmosphere;
General procedure: Scheme 6-4: In Step 1 the appropriately substituted and protected aniline is converted as known in the art to a sulfonamide. In Step 2 the appropriately substituted alcohol is converted as known in the art to a triflouro-sulfonamide. In Step 3 the previously prepared reagents are subjected to sodium hydride to afford their adduct. In Step 4 the appropriately substituted ketal is subjected to a strong lewis acid to afford deprotection and subsequent cyclization to a biaryl species. In Step 5 the appropriately substituted sulfonamide is deprotected in the presence of base to afford a free amine. In an alternative embodiment this synthetic protocol can be applied to other aniline isomers to afford substituents on alternative positions.
With pyridine; In dichloromethane;
In Step 1 the appropriately substituted and protected aniline is converted as known in the art to a sulfonamide. In Step 2 the appropriately substituted alcohol is converted as known in the art to a triflouro sulfonamide. In Step 3 the previously prepared reagents are subjected to sodium hydride to afford their adduct. In Step 4 the appropriately substituted ketal is subjected to a strong lewis acid to afford deprotection and subsequent cyclization to a biaryl species. In Step 5 the appropriately substituted sulfonamide is deprotected in the presence of base to afford a free amine. In an alternative embodiment this synthetic protocol can be applied to other aniline isomers to afford sub stituents on alternative positions.
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 5h;
Compound Va (45.0 g) was dissolved in dichloromethane (800 mL).2,2-Diethoxyethanol (26.0 g, available from Alpha Reagent) was added.4-dimethylaminopyridine (1.2g)And 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (24.2 g),React at 20 degrees for 5 hours,Add water to quench the reaction,The organic phase was dried over anhydrous sodium sulfate and concentrated.Column chromatography and purification gave compound IVa(35.0 g, yield 83percent).
12.1 g
With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃;
In a 250 ml reaction flask, compound II-5 acid crude was mixed with hydroxyacetaldehyde diethyl acetal (6.2 g, 2 eq.) and dissolved in dichloromethane (100 mL).1-Ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCI, 5.8 g, 1.3 eq.) and 4-dimethylaminopyridine (0.28 g, 0.1 eq.) were added thereto.,Stir at room temperature for 5 to 7 hours, add water to quench the reaction, separate, dilute with dichloromethane, and wash.After drying over anhydrous sodium sulfate, the crude product was concentrated under reduced pressure and purified by column chromatography to give the title compound II-6a (12.1 g, 90percent overall yield over two steps).
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