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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Dihydrofuran-3(2H)-one (3-Oxotetrahydrofuran) is a compound with an oxo-heterocyclic structure used in the synthesis of cyclic ketone inhibitors of serine protease plasmin.
Synonyms: 3-Oxotetrahydrofuran
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Batch number can be found on the product's label following the word 'Batch'.
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Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
Batch number can be found on the product's label following the word 'Batch'.
Search for reports by entering the product batch number.
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CAS No. : | 22929-52-8 |
Formula : | C4H6O2 |
M.W : | 86.09 |
SMILES Code : | O=C1CCOC1 |
Synonyms : |
3-Oxotetrahydrofuran
|
MDL No. : | MFCD07778393 |
InChI Key : | JLPJFSCQKHRSQR-UHFFFAOYSA-N |
Pubchem ID : | 529392 |
GHS Pictogram: |
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Signal Word: | Danger |
Hazard Statements: | H225-H315-H319 |
Precautionary Statements: | P501-P240-P210-P233-P243-P241-P242-P264-P280-P370+P378-P337+P313-P305+P351+P338-P362+P364-P303+P361+P353-P332+P313-P403+P235 |
Class: | 3 |
UN#: | 1224 |
Packing Group: | Ⅲ |
* 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 |
---|---|---|
80% | toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; | 1,4,7-Trioxaspiro[4.4]nonane. A mixture of intermediate 12 (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH.H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded intermediate 13 as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J=7.0 Hz), 3.94-3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J=7.0 Hz). |
80% | toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; | Intermediate 13l,4, 7~Trioxaspiro[4.4]nonane. A mixture of intermediate 12 (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH*H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded intermediate 13 as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J = 7.0 Hz), 3.94- 3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J = 7.0 Hz). |
80% | toluene-4-sulfonic acid; In benzene; for 17h;Heating / reflux; | 1,4,7-Trioxaspiro[4.4]nonane. A mixture of ethyl 3'-hydroxy-4'-oxo-6',7'-dihydro-4'H-spiro[cyclopentane-1,9'-pyrimido[2,1-c][1,4]oxazine]-2'-carboxylate (15.79 g, 183.5 mmol), ethylene glycol (16.7 mL, 300 mmol) and cat. TsOH.H2O (100 mg) in benzene (100 mL) was heated at reflux using Dean-Stark trap. After 17 h, the reaction mixture was cooled, diluted with ether (150 mL), washed with sat. Na2CO3 and brine (50 mL each), dried (Na2SO4), filtered and concentrated to give yellow liquid. Distillation under reduced pressure afforded the title compound as a yellow liquid (19.13 g, 80percent). 1H NMR (500 MHz, CDCl3) delta: 3.9.4 (2H, t, J=7.0 Hz), 3.94-3.90 (4H, m), 3.68 (2H, s), 2.09 (2H, t, J=7.0 Hz). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; | To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent). |
95% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; | To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent). |
95% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical; trichloroisocyanuric acid; In dichloromethane; at -5 - 20℃; for 1h; | To a 1 L flask, 3-tetrahydrofuran (3-OH-THF, 60.6 g, 0.68 mol, 1 equ.) was charged, followed by DCM (620 mL) and TEMPO(1.08 g, 0.0069 mol, 0.01 equ.) The solution was cooled to -5 °C. To which TCCA (159.6 g, 0.68 mol, 1 equ.) was added in portions controlling the tern- perature around -5 °C to 0 °C. The resulting mixture was allowed to warm to rt and monitored by GC-MS, Reaction was finished in 1 h to give 95percent yield (GC areapercent). |
79% | With pyridinium chlorochromate; In dichloromethane; at 20℃; | Description 20 : Dihydro-3(2H)-furanone; A mixture of 3-hydroxytetrahydrofuran (3.0 g, 0.034 mol) and pyridinium chlorochromate (14.7 g, 0.068 mol) in DCM (100 ml) was stirred at room temperature overnight. The title product was obtained by pouring the crude product through a silica pad using ethyl acetate as the eluent. The title product was obtained from 2 elutions (2.29 g; 79percent). 1H NMR (CDCI3) delta: 2.50 (2H, t), 3.87 (2H, s), 4.26 (2H, t). |
60% | With acetic acid; pyridinium chlorochromate; In dichloromethane; at 20℃;Molecular sieve; Inert atmosphere; | Pyridinium chlorochromate (6.5 g, 30 mmol, 1.5 equiv) was dissolved in 100 ml DCM at rt. Tetrahydro-3-furanol (1.6 ml, 20 mmol, 1 equiv) was added dropwise. 4 A molecular sieves (16 g) and glacial acetic acid (2 ml) were respectively added. The reaction mixture was stirred at rt overnight. A generous amount of Celite ® 545 was added and the solvent was removed by reduced pressure. The residue was then passed through a Celite ® 545 plug (10percent dichloromethane/diethyl ether) and the solvent was removed in vacuo. The residue was then purified by flash column chromatography (10percent dichloromethane/diethyl ether) to afford 3.45 (60percent yield). Spectral data correspond to that reported.24 1H NMR (400 MHz, CDCI3): delta 4.24 (t, J = 7.3 Hz, 2 H), 3.86 (s, 2 H), 2.48 (t, J = 7.3 Hz, 2 H). |
With pyridinium chlorochromate; In dichloromethane; at 20℃; for 3.5h; | Pyridinium chlorochromate (85.8 g, 3.5 eq) was added in portions over a period of 5 minutes to a solution of 3-hydroxytetrahydrofuran (10.02 g, 1.0 eq) in dichloromethane (115 mL). The reaction mixture was stirred at ambient temperature for 3.5 hours and then applied directly to a column of silica gel (325 g). The column was eluted with diethyl ether. The fractions containing product were combined and the solvent was removed by atmospheric distillation to provide 5.22 g of tetrahydrofuran-3-one | |
With pyridinium chlorochromate; In dichloromethane; at 40℃; for 16h; | 00182] Step 2: To a solution of tetrahydrofuran-3-ol (92.5 g, 1.05 mol) indichloromethane (2000 mL) was added pyridinium chlorochromate (454 g, 2.10 mol) and silicon gel (500 g). The reaction mixture was heated to 40°C. After 16 hours, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the crude residue. The residue was purified via chromatography on silica gel (methanol/DCM, linear gradient) to afford dihydrofuran-3(2H)-one. | |
With silica gel; pyridinium chlorochromate; In dichloromethane; at 40℃; for 16h; | To a solution of tetrahydrofuran-3-ol (92.5 g, 1.05 mol) indichloromethane (2000 mL) was added pyridinium chlorochromate (454 g, 2.10 mol) and silica gel (500 g). The reaction mixture was heated to 40°C. After 16 hours, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to afford the crude residue. The residue was purified via chromatography on silica gel (methanol/DCM, linear gradient) to afford dihydrofuran-3(2H)-one. | |
With pyridinium chlorochromate; In dichloromethane; at 0 - 20℃; | b) dihydrofuran-3(2H)-one To a stirred solution of tetrahydrofuran-3-ol (3.0 g, 34 mmol) as obtained in step a) in DCM (60 mL) was added pyridiniumchloro chromate (14.65 g, 68 mmol) at 0 °C and the reaction mixture was stirred at rt for 16 h. Once the starting material was consumed (monitored by TLC), the reaction mixture was filtered through celite and the filtrate was washed with water, brine, drier over anhydrous Na2S04 and concentrated. The crude product (2.5 g) was used in the next step without further purification. | |
With tetrapropylammonium perruthennate; 4-methylmorpholine N-oxide; In dichloromethane; at 20℃; for 2h;Molecular sieve; | Tetrapropylammonium perruthenate (TPAP, 20 mg, 0.057 mmol) was added to a mixture of tetrahydrofuran-3-ol (616 mg, 7.0 mmol), N-methylmorphorine N-oxide (NMO, 11 mmol), activated molecular sieve powder (3.5 g) in dichloromethane (30 mL) at room temperature, the reaction mixture was stirred at room temperature for 2 h, then filtered through a short pad of Celite under reduced pressure. The EPO <DP n="85"/>dichloromethane solution ( 20 mL) of dihydrofuran-3(2H)-one was used as a stock solution (0.3 M). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85-105% | Dihydro-3(2H)-furanone (18, 24-28), (1.0 eq) was dissolved in a mixture of ethanol/water (7:1 v/v, 10 mL per mmole compound) containing sodium acetate trihydrate (1.5 eq). 4-[[(hydrazinocarbonyl)amino]methyl]-cyclohexanecarboxylic acid trifluoro acetate (mw 329.3, 1.0 eq) (see Murphy, A. M., et al, J. Am. Chem. Soc, 114, 3156-3157, 1992) was added and the mixture heated under reflux for 2 hrs. The mixture was then cooled, poured into dichloromethane (100 mL per mmole compound) and water (100 mL) added. The organic layer was separated, backwashed with saturated brine (100 mL). The organic layer was dried (Na2SO4), filtered and evaporated in vacuo to yield a white solid. Yield 85-105percent crude weight. Constructs (29-34) were used without further purification | |
Step E Cleavage A mixture of 7:2:1 TFA/CH2Cl2/H2O was added to the above resin. After 2 hours, the mixture was filtered and the resin was further washed with CH2Cl2. Removal of the solvent afforded the desired tetrahydrofuran-3-one. |