* 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 hydrogen; sodium acetate In methanol at 40℃; for 8 h;
4,5-Dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one (280 kg, 843mol), anhydrous sodium acetate (173 kg, 2109 mol), methanol (6384 L) were mixed, and the reaction system was replaced with nitrogen. Then, to the reaction mixture was added 10percent Pd/C (30.8 kg, as dry weight), and pressurized with hydrogen to 0.29 to 0.49 MPa, and catalytically reduced at about 40°C for 8 hrs with stirring at such a stirring rate that the gas-liquid overall mass transfer coefficient KLa(1/hr) is about 15. The catalyst was filtered, and the filtrate was concentrated under reduced pressure, and further water was added to the residue, followed by concentrating under reduced pressure to substitute the solvent, cooling and stirring for 1 hr to mature. The crystallization solution was filtered to give wet crystals of title compound (amount 127 kg as dry weight, yield 86.6percent). The content of dimer in the wet crystals was less than 0.1percent by weight.
83%
With sodium acetate In methanol
Reference Example 6 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one To a suspension of 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one (18.4 g, 55.4 mmols) in methanol (400 mL) was added 10percent Palladium on activated carbon (2.0 g, 50percent hydrous) followed by sodium acetate (12.6 g, 154 mmols). The mixture was stirred at 40° C. for 1.5 hours under hydrogen atmosphere (4 kgf/cm2). The catalyst was filtered off and the filtrate was concentrated under reduced pressure. Crystals were collected by filtration, washed with water and recrystallized successively with methanol:water=5:1 to obtain 8.0 g (yield: 83percent) of the title compound.
83%
With hydrogen; sodium acetate In methanol; acetic acid at 20℃; for 2 h;
To a suspension of 4,5-dibromo-l,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one (720 g, 2.15 moles) in methanol (6.60 lit.) and acetic acid (1.5 lit.) was added 10percent palladium on activated carbon (150 g, 50percent hydrous) followed by addition of sodium acetate (500 g, 6.09 moles). The reaction mixture was stirred at room temperature for 2 hours under hydrogen atmosphere (5 kg/cm2). After the completion of reaction, the catalyst was filtered off and the filtrate was concentrated under reduced pressure. The obtained crystals were collected by filtration, washed with water (3 lit.) and recrystallized with methanol-water (5:1) to obtain 318 g (83percent yield) of the title compound.
With hydrogen In tetrahydrofuran; ethanol at 35℃; for 24 h;
6,7-dihydro-8H-indeno-[5,4-b]furan-8-one of the formula (IV) (2.0 g, 11.6 mmol) was dissolved in a solvent mixture (40 ml ethanol, 20 ml tetrahydrofuran and 12 drops of triethylamine). The stirred solution was hydrogenated for 24 hours at 35 °C/0.6-0.7 MPa over Pd-C (500 mg, 5 percent Pd-C (w/w)). The progress of reaction was monitored with HPLC. After the reaction was completed, the hydrogen gas was released, Pd-C was filtered off and the product was washed with 20 ml THF. After removal of the solvent under vacuum, recrystallization from ethanol afforded 1 ,2,6,7-tetrahydro-8 - -indeno- [5,4-b]furan-8-one of the formula (I) as light yellow solid (yield 62 percent, 99.6 HPLC purity). 1H NMR (CDCI3, 400 MHz), δ: 7.22 (d, J = 8.4 Hz, H), 7.03 (d, J = 8.4 Hz, 1 H), 4.67 (t, J = 8.8 Hz, 2H), 3.49 (t, J = 8.8 Hz, 2H,), 3.10 (t, J = 5.2 Hz, 2H), 2.70 (t, J = 5.2 Hz, 2H) 13C NMR (CDCI3, 100 MHz), δ: 207.42, 160.25, 147.11 , 133.68, 125.62, 123.93, 115.63, 72.34, 37.16, 28.41 , 25.40Retention time (LC/MS), min: 8.38; MS (MH+), m/z: 173; Molecular weight, g/mol: 174.
In methanol;Heating / reflux;Purification / work up;
Example 8:Synthesis of Intermediate VIII:The compound of formula VII (100.0 g, 0.3012 mol), sodium acetate (61.75 g, 0.753 mol), and 10percent Pd/C (10.0 g) in acetic acid (1000 ml) were stirred under a hydrogen atmosphere (2-3 kg/cm2). The reaction progress was monitored by HPLC. The reaction mixture was filtered through a filter aid (CELITE HYFLO.(TM).), and the acetic acid was removed under vacuum at 50-600C. The solid product was isolated by filtration and dried under vacuum at 50-600C. Yield: 85-90percent Purity: 96-97percent. For Impurity VIII A : H1 NMR:2.01-2.11 2H t ; 2.756-3.058 HH m ; 3.101-3.340 2H t ; 4.500-4.542 2H t ; 6.562-6.582 IH d ; 6.929-6.949 IH d <n="50"/>C13 NMR:25.92, 28.72, 31.36, 32.11, 71.21, 106.70, 122.55, 122.92, 136.29, 140.86, 158.91For Impurity VIII B: H1 NMR:1.87-1.93, IH, m ; 2.12-2.13, IH, d ; 2.40-2.48, lH,m ; 2.65-2.73, IH, m ; 2.89-2.97, IH, m ; 3.07-3.15, IH, m ; 3.23-3.32, IH, m ; 4.49-4.54, 2H, m ; 5.15-5.18,1H, t ; 6.64- 6.66, IH, d ; 6.92-6.94 IH, d) C13 NMR:Purification of Intermediate VIII:Crude compound of formula VIII (100 g) was heated to reflux in methanol (1500 ml) to produce a clear solution. This clear solution was decolorized by charcoal treatment with stirring at reflux temperature. The reaction mixture was filtered while hot through a filter aid (CELITE HYFLO.(TM).), and the filtrate was concentrated and then cooled to 10-15 0C and stirred for 1-2 hr. The product was collected by filtration, washed with cold methanol, and dried under reduced pressure at 50-600C. Yield: 80- 85percent, Purity: 99.2-99.8percent.
Reference Example 18 1,2,6,7-Tetrahydro-8H-indeno[5,4-b]furan-8-one 5percent Palladium carbon (50percent hydrous, 2.9 g) and sodium acetate (17.9 g, 0.22 mol) were added to a solution of 4,5-dibromo-1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8- one (29.0 g, 87.4 mmol) in acetic acid (550 ml), and the mixture was catalytically reduced in a hydrogen atmosphere at ordinary temperature and ordinary pressure. After absorption of the calculated amount of hydrogen, the palladium carbon was filtered off and the solvent was distilled off under reduced pressure. Water was added to the residue and the organic matter was extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium bicarbonate solution, a saturated aqueous sodium chloride solution and water and then dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue obtained was purified by silica gel column chromatogarphy (ethyl acetate:hexane=15:85) to give the target compound. The yield was 13.5 g (89percent). m.p.: 133-134° C. (recrystallized from ethyl acetate/hexane); NMR (CDC13) delta: 2.68 (2H, t, J=5.9 Hz), 3.08 (2H, t, J=5.9 Hz), 3.47 (2H, t, J=8.8 Hz) 4.65 (2H, t, J=8.8 Hz), 7.01 (1H, d, J=8.1 Hz), 7.21 (1H, d, J=8.1 Hz); Elemental Analysis for C11 H10 O2: Calcd.: C 75.84; H 5.79; Found: C 75.69; H 5.75
19
sodium methoxide methanol[ No CAS ]
[ 2537-48-6 ]
[ 196597-78-1 ]
[ 196597-79-2 ]
Yield
Reaction Conditions
Operation in experiment
In methanol; water; toluene;
Reference Example 7: Synthesis of (E)-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-ylidene)acetonitrile To a solution of toluene (184 g), <strong>[196597-78-1]1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one</strong> (8.5 g, 48.9 mmol) and diethyl cyanomethylphosphonate (10.4 g, 58.7 mmol), 28percent sodium methoxide methanol solution (11.3 g) was added dropwise with ice cooling over one hour and the reaction was conducted for 4 hours. Water (85 g) was added dropwise to the reaction mixture and, after heating and partitioning, the organic layer was washed with water and then filtered under pressure to remove dusts. The organic layer was concentrated under reduced pressure and methanol was added, followed by concentration under reduced pressure to effect replacement of the solvent. The mixture was stirred with heating under reflux for one hour, followed by cooling and aging for one hour. The mixture containing the deposited crystals was filtered and the crystals were dried under reduced pressure to obtain the title compound (yield: 8.1 g, 84.4percent).
In methanol; water; toluene;
REFERENCE EXAMPLE 7 Synthesis of (E)-(1,6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-ylidene)acetonitrile To a solution of toluene (184 g), <strong>[196597-78-1]1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one</strong> (8.5 g, 48.9 mmol) and diethyl cyanomethylphosphonate (10.4 g, 58.7 mmol), 28percent sodium methoxide methanol solution (11.3 g) was added dropwise with ice cooling over one hour and the reaction was conducted for 4 hours. Water (85 g) was added dropwise to the reaction mixture and, after heating and partitioning, the organic layer was washed with water and then filtered under pressure to remove dusts. The organic layer was concentrated under reduced pressure and methanol was added, followed by concentration under reduced pressure to effect replacement of the solvent. The mixture was stirred with heating under reflux for one hour, followed by cooling and aging for one hour. The mixture containing the deposited crystals was filtered and the crystals were dried under reduced pressure to obtain the title compound (yield: 8.1 g, 84.4percent).
Wet crystals (127 kg as dry weight), activated charcoal (6 kg, Shirasagi A: trade name) and methanol (1723 L) were mixed, and stirred for 1 hr under reflux, and filtered. The filtrate and washings were concentrated under reduced pressure, then, the residue was refluxed for 1 hr and cooled. Water (306 L) was added thereto under cooling, matured for 1 hr, and the precipitate was collected by filtration, followed by drying under reduced pressure to give title compound (amount 117 kg, yield 92.1percent).
21
[ 2537-48-6 ]
[ 196597-78-1 ]
[ 221530-44-5 ]
Yield
Reaction Conditions
Operation in experiment
80%
Sodium methoxide (7.8 g, 144 mmol) was added to a solution of diethyl cyanomethyl- phosphonate (22 g, 126 mmol) in THF (60 ml) at ambient temperature. The mixture was stirred for an hour. The resulting solution was added dropwise to a solution of I ^^J-tetrahydro-SH-indenotS^-felfuran-e-one of the formula (I) (15.7 g, 90 mmol) in THF (60 ml) over 15 min at room temperature. This reaction mixture was stirred for 2.0 hours and subsequently quenched with water (150 ml). THF was evaporated and the product was extracted with ethyl acetate. The combined organic phase was evaporated under vacuum to afford a yellow solid (22 g). Recrystallization from a solvent mixture (ethyl acetate/hexane = 2/1 (v/v)) gave 10,1 g 2-(1 ,2,6,7-tetrahydro-8 - -indeno- [5,4-/}]furan-8-ylidene)acetonitrile as light yellow solid. The mother liquor was concentrated, and was recharged to retry the above reaction. In the following, additional 4.5 g 2-(1 ,2,6,7-tetrahydro-8H-indeno[5,4-i ]furan-8-ylidene)acetonitrile was obtained (yield 80 %, 96.5 HPLC purity).1H NMR (CDCI3, 400 MHz), delta: 7.09 (d, J = 8.4Hz, 1 H), 6.84 (d, J = 8.4 Hz, 1 H), 5.44 (t, J = 2.4 Hz, 1 H), 4.65 (t, J = 8.8 Hz, 2H), 3.29 (t, J = 8.8 Hz, 2H), 3.12-3.09 (m, 2H), 3.03 (t, J = 5.2 Hz, 2H)13C NMR (CDCI3, 100 MHz), delta: 167.76, 160.16, 142.25, 134.97, 124.84, 121.91 , 118.14, 112.98, 87.93, 71.43, 32.41 , 29.31 , 29.11Retention time (LC/MS), min: 9.94; MS (MH+), m/z: 197; Molecular weight, g/mol: 197
5.1 kg
the Tetrahydrofuran (22 L) and 60% NaH (2 kg) were added to a 50 L double glass reactor and stirred evenly at 25 C. A solution of diethyl cyanomethylphosphonate (14 kg) was added dropwise and stirred for 1 hour to give a clear Ylide solution. in other hand, tetrahydrofuran (22 L) and 1,2,6,7-tetrahydro-8H-indeno [5,4-b] furan-8-one (compound of formula (I)) (4kg) were added to a 100 L double glass reactor and stir well. The fresh prepared Ylide solution was added dropwise to the system. After stirring for 3 hours, water (22 L) was slowly added to the reaction system. After addition, stirring was continued for 30 minutes. The reaction solution was poured into water (202 L) and stirring was continued for 1 hour. Filtered to give 5.1 kg of 1,6,7,8-tetrahydro-2H-indeno [5,4-b] furan-8-ylideneacetonitrile (formula (II) compound).
In methanol; at 20℃; for 0.25h;Alkaline conditions;
50.0 g of 6,7-dihydro-1H-indeno [5,4-b] furan-8 (2H) -one and 1425 ml of methanol were added at room temperature2000ml single mouth bottle,Then 65.0 g of anhydrous sodium formate was added,After stirring for 15 min,A solution of 2- (diethoxyphosphoryl) acetonitrile was added dropwise.TLC to the compound (1) The reaction was complete, 700 ml of deionized water was added, stirred,The filter cake is compound (2).
With sodium methylate; at 5 - 25℃;
EXAMPLE 10: Preparation of 2-(1 ,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8- ylidene)acetonitrile (FORMULA V, wherein "**** represents a single bond); 53 g of 1 ,2,6,7-tetrahydro-8H-indano[5,4-b]furan-8-one of Formula Vl (wherein """^ represents a single bond), and toluene 1325 ml were charged into <n="34"/>an clean and dry 4 neck round bottom flask followed by stirring and cooling given. To the above solution 89.1 g of diethylcyanomethyl propionate was slowly added at 50C and then 73.1 g of sodium methoxide was slowly added to the reaction mass at about 10-120C. The resultant reaction mixture was stirred at 250C till the completion of the reaction. The resultant reaction mass was quenched by addition of 530 ml of water followed by stirring for about 10 minutes. Organic and aqueous layers were separated. The aqueous layer was extracted with toluene 100 ml. Combined both the organic layers and completely distilled under vacuum at below 600C to obtain the residue. 265 ml of water was added to the residue followed by stirring for 30 minutes. The separated solid was filtered and washed with water. The obtained solid was dried under vacuum at 500C to a constant weight to afford 58 g of the title compound.
With hydrogen; sodium acetate; acetic acid;palladium 10% on activated carbon; under 1471.14 - 2206.72 Torr;
Example 8:Synthesis of Intermediate VIII:The compound of formula VII (100.0 g, 0.3012 mol), sodium acetate (61.75 g, 0.753 mol), and 10% Pd/C (10.0 g) in acetic acid (1000 ml) were stirred under a hydrogen atmosphere (2-3 kg/cm2). The reaction progress was monitored by HPLC. The reaction mixture was filtered through a filter aid (CELITE HYFLO), and the acetic acid was removed under vacuum at 50-600C. The solid product was isolated by filtration and dried under vacuum at 50-600C. Yield: 85-90% Purity: 96-97%. For Impurity VIII A : H1 NMR:2.01-2.11 2H t ; 2.756-3.058 HH m ; 3.101-3.340 2H t ; 4.500-4.542 2H t ; 6.562-6.582 IH d ; 6.929-6.949 IH d <n="50"/>C13 NMR:25.92, 28.72, 31.36, 32.11, 71.21, 106.70, 122.55, 122.92, 136.29, 140.86, 158.91For Impurity VIII B: H1 NMR:1.87-1.93, IH, m ; 2.12-2.13, IH, d ; 2.40-2.48, lH,m ; 2.65-2.73, IH, m ; 2.89-2.97, IH, m ; 3.07-3.15, IH, m ; 3.23-3.32, IH, m ; 4.49-4.54, 2H, m ; 5.15-5.18,1H, t ; 6.64- 6.66, IH, d ; 6.92-6.94 IH, d) C13 NMR:Purification of Intermediate VIII:Crude compound of formula VIII (100 g) was heated to reflux in methanol (1500 ml) to produce a clear solution. This clear solution was decolorized by charcoal treatment with stirring at reflux temperature. The reaction mixture was filtered while hot through a filter aid (CELITE HYFLO), and the filtrate was concentrated and then cooled to 10-15 0C and stirred for 1-2 hr. The product was collected by filtration, washed with cold methanol, and dried under reduced pressure at 50-600C. Yield: 80- 85%, Purity: 99.2-99.8%.
Example 9:Synthesis of Intermediate X:A 60percent suspension of sodium hydride in mineral oil (34.4 g, 1.43 mol) was added to dry toluene (3000 ml) under a nitrogen atmosphere, cooled, and stirred at 0- 50C for 15-20 minutes. Triethyl phosphonoacetate (257.1 g, 1.148 mol) was added dropwise at 0-50C and stirred for 2 hr at room temperature. Compound VIII (100.0 g, 0.5740 mol) was added, and the reaction mixture was heated to 90-1000C and stirred under a nitrogen atmosphere for 15-18 hr. The reaction was monitored by HPLC. After completion of the reaction, the mixture was cooled and water was added slowly with striring. The organic layer was separated, washed with brine, and concentrated under vacuum at 50-60° C to leave crude product. Yield: 80-85percent, Purity: 92-95percent.
Example-1; Synthesis of Intermdiate-IIA 60percent suspension of sodium hydride in mineral oil (34.4 g, 1.43 mol) was added to dry toluene (3000 ml) under a nitrogen atmosphere, cooled, and stirred at 0-5° C. for 15-20 minutes. Triethyl phosphonoacetate (257.1 g, 1.148 mol) was added dropwise at 0-5° C. and stirred for 2 hr at room temperature. <strong>[196597-78-1]1,2,6,7-tetrahydro-8H-indeno[5,4-b]furan-8-one</strong> (100.0 g, 0.5740 mol) was added, and the reaction mixture was heated to 90-100° C. and stirred under a nitrogen atmosphere for 15-18 hr. The reaction was monitored by HPLC. After completion of the reaction, the mixture was cooled and water was added slowly with stirring. The organic layer was separated, washed with brine, and concentrated under vacuum at 50-60° C. to leave crude product. Yield: 80-85percent, Purity: 92-95percent (By HPLC).
With sulfuric acid; In pentane; at 67℃;Inert atmosphere;Product distribution / selectivity;
Example 3:Preparation of 6,7-dihydro-1 H-indeno[5,4-b]furan-8(2H)-one (V)12 II I V1-(2,3-dihydrobenzofuran-4-yl)ethanone (III) (1 g, 6,2 mmol) was dissolved in dioxane (9 ml_). TADCA (dicyclohexylammonium 2,2,2-trifluoroacetate) (1 ,82 g, 1 eq) and paraformaldehyde (0,611 g, 1 ,1 eq) were added. The reaction was heated at 100°C for 2 h. A second portion of TADCA (0,91 g, 0,5 eq) and paraformaldehyde (0,333 g, 0,6 eq) were added and the reaction was heated at 100°C for 2 h. Reaction was partitioned between water (20 ml_) and pentane (30 ml_). Aqueous phase was re-extracted 4 times with pentane (10 ml_). Combined pentane phases were washed with water and brine, dried over MgSO4. Solution was diluted to 100 ml_ with pentane. This solution was added dropwise to a pre-heated solution of sulfuric acid at 67°C (10 ml_) under nitrogen stream. At the end of addition, the reaction was stirred for 30 min. Reaction was cooled down to room temperature and poured on iced water (50 ml_). Solution was extracted 5 times with MTBE. Combined organic phases were washed with water, NaHCO3 1 M and brine, dried over MgSO4 and concentrated. Purification by flash chromatography furnished pure 6,7-dihydro-1 H- indeno[5,4-b]furan-8(2H)-one. 1H NMR delta (CDCI3) 7,21 (dd, 1 H, J = 0,9 Hz, J = 9,0 Hz), 7,02 (d, 1 H, J = 8,2 Hz), 4,66 (t, 2H, J = 8,9 Hz), 3,48 (t, 2H, J = 8,9 Hz), 3,08 (dd, 2H, J = 4,9 Hz, J = 6,0 Hz), 2,69 (m, 2H). 13C NMR delta (CDCI3) 207,5, 160,2, 147,1 , 133,6, 125,6, 123,9, 115,6, 72,3, 37,1 , 28,4, 25,4.
With sulfuric acid; In water; pentane; at 67℃; for 0.5h;Inert atmosphere;
Example 3:Preparation of 6,7-dihydro-1 H-indeno[5,4-b]furan-8(2H)-one (V) 1-(2,3-dihydrobenzofuran-4-yl)ethanone (III) (1 g, 6.2 mmol) was dissolved in dioxane (9 ml). TADCA (dicyclohexylammonium 2,2, 2-trifluoroacetate) (1.82 g, 1 eq) and paraformaldehyde (0.611 g, 1.1 eq) were added. The reaction was heated at 1000C for 2 h. A second portion of TADCA (0.91 g, 0.5 eq) and paraformaldehyde (0.333 g, 0.6 eq) were added and the reaction was heated at 1000C for 2 h. Reaction was partitioned between water (20 ml) and pentane (30 ml). Aqueous phase was re- extracted 4 times with pentane (10 ml). Combined pentane phases were washed with water and brine, dried over MgSO4. Solution was diluted to 100 ml with pentane. This solution was added dropwise to a pre-heated solution of sulfuric acid at 670C (10 ml) under nitrogen stream. At the end of addition, the reaction was stirred for 30 min. Reaction was cooled down to room temperature and poured on iced water (50 ml). Solution was extracted 5 times with MTBE. Combined organic phases were washed with water, NaHCO3 1 M and brine, dried over MgSO4 and concentrated. Purification by flash chromatography furnished pure 6,7-dihydro-1 H-indeno[5,4-b]furan-8(2H)-one (V). 1H NMR delta (CDCI3) 7.21 (dd, 1 H, J = 0.9 Hz, J = 9.0 Hz), 7.02 (d, 1 H, J = 8.2 Hz), 4.66 (t, 2H, J = 8.9 Hz), 3.48 (t, 2H, J = 8.9 Hz), 3.08 (dd, 2H, J = 4.9 Hz, J = 6.0 Hz), 2.69 (m, 2H). 13C NMR delta (CDCI3) 207.5, 160.2, 147.1 , 133.6, 125.6, 123.9, 115.6, 72.3, 37.1 , 28.4, 25.4.
Example 4:Preparation of 6,7-dihydro-1 H-indeno[5,4-b]furan-8(2H)-one (Vl)V Vl1 -(2,3-dihydrobenzofuran-4-yl)ethanone (V) (1 g, 6.2 mmol) was dissolved in dioxane (9 ml). TADCA (dicyclohexylammonium 2,2,2-trifluoroacetate) (1 .82 g, 1 eq) and paraformaldehyde (0.61 1 g, 1.1 eq) were added. The reaction was heated at 1000C for 2 h. A second portion of TADCA (0.91 g, 0.5 eq) and paraformaldehyde (0.333 g, 0.6 eq) were added and the reaction was heated at 1000C for 2 h. Reaction was partitioned between water (20 ml) and pentane (30 ml). Aqueous phase was re-extracted 4 times with pentane (10 ml). Combined pentane phases were washed with water and brine, dried over MgSO4. Solution was diluted to 100 ml with pentane. This solution was added dropwise to a pre-heated solution of sulfuric acid at 67°C (10 ml) under nitrogen stream. At the end of addition, the reaction was stirred for 30 min. Reaction was cooled down to room temperature and poured on iced water (50 ml). Solution was extracted 5 times with MTBE. Combined organic phases were washed with water, NaHCO3 1 M and brine, dried over MgSO4 and concentrated. Purification by flash chromatography furnished pure 6,7-dihydro-1 H-indeno[5,4-b]furan-8(2H)-one (Vl). 1H NMR delta (CDCI3) 7.21 (dd, 1 H, J = 0.9 Hz, J = 9.0 Hz), 7.02 (d, 1 H, J = 8.2 Hz), 4.66 (t, 2H, J = 8.9 Hz), 3.48 (t, 2H, J = 8.9 Hz), 3.08 (dd, 2H, J = 4.9 Hz, J = 6.0 Hz), 2.69 (m, 2H). 13C NMR delta (CDCI3) 207.5, 160.2, 147.1 , 133.6, 125.6, 123.9, 1 15.6, 72.3, 37.1 , 28.4, 25.4.
With hydrogen;5% Pd(II)/C(eggshell); triethylamine; In tetrahydrofuran; ethanol; at 35℃; under 4500.45 - 5250.53 Torr; for 24h;
6,7-dihydro-8H-indeno-[5,4-b]furan-8-one of the formula (IV) (2.0 g, 11.6 mmol) was dissolved in a solvent mixture (40 ml ethanol, 20 ml tetrahydrofuran and 12 drops of triethylamine). The stirred solution was hydrogenated for 24 hours at 35 °C/0.6-0.7 MPa over Pd-C (500 mg, 5 percent Pd-C (w/w)). The progress of reaction was monitored with HPLC. After the reaction was completed, the hydrogen gas was released, Pd-C was filtered off and the product was washed with 20 ml THF. After removal of the solvent under vacuum, recrystallization from ethanol afforded 1 ,2,6,7-tetrahydro-8 - -indeno- [5,4-b]furan-8-one of the formula (I) as light yellow solid (yield 62 percent, 99.6 HPLC purity). 1H NMR (CDCI3, 400 MHz), delta: 7.22 (d, J = 8.4 Hz, H), 7.03 (d, J = 8.4 Hz, 1 H), 4.67 (t, J = 8.8 Hz, 2H), 3.49 (t, J = 8.8 Hz, 2H,), 3.10 (t, J = 5.2 Hz, 2H), 2.70 (t, J = 5.2 Hz, 2H) 13C NMR (CDCI3, 100 MHz), delta: 207.42, 160.25, 147.11 , 133.68, 125.62, 123.93, 115.63, 72.34, 37.16, 28.41 , 25.40Retention time (LC/MS), min: 8.38; MS (MH+), m/z: 173; Molecular weight, g/mol: 174.
Example 1; Synthesis of (1, 6,7,8-Tetrahydro-2H-indeno-[5,4-b]furan-8-ylidene) -acetonitrile; l,2,6,7-Tetrahydro-8H-indeno-[5,4-b]furan-8-one (100 gm, 0.5747 mol ) and cyano acetic acid ( 75 gm, 0.8823 mol ) were added in piperidine (400 ml ) at ambient temperature. The reaction mass was heated to 100-110C and then cooled to 55C and the piperidine was removed under reduced pressure below 55C. Water (500 ml) was added to the residue and extracted with dichloromethane (3 X 500 ml). Organic layer was washed with brine and distilled under reduced pressure below 50C. The solid was stirred in heptane (500 ml), filtered, washed with heptane and dried under vacuum at 50-60C to give 106 gms of the title compound.Yield:- 93%
With sodium methylate; In methanol; toluene; at 50 - 60℃;Inert atmosphere;
Example 7; Synthesis of N-[2-(l6,7,8-Tetrahydro-2H-indeno[5,4-b]furan-8-ylidene) ethyl] pro ionamide; To a stirred solution of 1, 2,6,7-Tetrahydro-8H-indeno-[5,4-b]furan-8-one (100 gm, 0.5747 mol)and Diethyl(2-ethyl propionamide)phosphonate ( 204 gm, 0.8620 mol ) in toluene (1000 ml) at ambient temperature under inert atmosphere, were charged solution of sodium methoxide ( 62 gm, 1.1494 mol ) in methanol ( 100 ml). The reaction mass was heated to 50-60°C for 4-5 hrs, cooled to 40-50°C and toluene was removed under reduced pressure. Water (500 ml) was added to the residue and extracted with dichloromethane (3 X 500 ml). The organic layer was washed with brine and distilled of under reduced pressure below 50°C. The residue was stirred in heptane (500 ml) for 2 hrs at ambient temperature, filtered, washed with heptane (2 X 50 ml) and dried under vacuum at 50-60°C to give 85 gms of the title compound.Yield: - 57.5percent
15.0 g of compound I,5.64 g of malononitrile,2.26 g of ammonium acetate and 4.5 mL of acetic acid were dissolved in 115 mL of toluene,TLC detection reaction is complete,The liquid phase poured out,And washed with water and brine,Dried over anhydrous magnesium sulfate,filter,In addition to solvent,Resulting in 15.66 g of compound IIA,Yield: 91.2percentNo further processing can be done directly.
2,6,7,8-tetrahydro-1H-indeno[5,4-b]furan-8-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium tert-butylate; In 1,2-dimethoxyethane; ethanol; at 0 - 60℃; for 18h;
The compound of formula 15-1 (174 mg, 1 mmol, its synthesis method is shown in US6034239A1, 2000) was dissolved in dry DME (ethylene glycol dimethyl ether) (6 mL),TosMIC (methylbenzenesulfonylmethylisonitrile) (648 mg, 2.2 mmol) was added, cooled to 0° C. in an ice water bath, ethanol (0.08 mL, 2.2 mmol) and potassium tert-butoxide (246 mg, 2.2 mmol) were added, and the temperature was increased. Stir at 60°C for 18 hours, warm up at 60°C for 18 hours,Cool and concentrate to remove the organic solvent. Add ethyl acetate to dissolve the residue. Wash with saturated brine, dry over sodium sulfate, spin-dry, and column chromatography to obtain a yellow solid, compound of Formula 10-2 (176 mg, 95percent).
Chemistry
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Material Science
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110K+ Compounds
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