Structure of 95091-92-2
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CAS No. : | 95091-92-2 |
Formula : | C7H9NO3 |
M.W : | 155.15 |
SMILES Code : | O=C(C1=CC=CO1)N(OC)C |
MDL No. : | MFCD06804576 |
InChI Key : | ZPMBEUDMVUSUOS-UHFFFAOYSA-N |
Pubchem ID : | 10820793 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 |
* 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 |
---|---|---|
87.2% | With pyridine; In chloroform; at 0 - 20℃; | 2-Furoyl chloride (40 mL, 0.406 mol) was dissolved in 800 mL of EtOH free CHCl3 (washed with H2O (3×) then dried (Na2SO4)) with N,O-dimethylhydroxylamine hydrochloride (43.6 g, 0.446 mol, 1.10 eq) and cooled to 0 C. Pyridine (66 mL, 0.816 mol, 2.0 eq) was added portion-wise and the mixture was stirred (15 min.) then warmed to rt overnight. The reaction mixture was then evaporated and the residue was partitioned between Et2O (400 mL) and brine (400 mL) then separated. The aqueous layer was extracted with Et2O (1×) and the combined organics are dried (Na2SO4), filtered, and evaporated to afford crude amide (54.8 g, 0.353 mol, Yld. 87.2%) that was taken on to the next step without further purification. 1H NMR: δ 7.54 (dd, 1H, 3JH,H=1.7 Hz, 4JH,H=0.70 Hz, H-2), 7.10 (dd, 1H, JH,H=3.5 Hz, 4JH,H=0.70 Hz, H-4), 6.46 (dd, 1H, 3JH,H=1.7 Hz, 3JH,H=3.5 Hz, H-3), 3.71 (s, 3H, N-OCH3), 3.30 (s, 3H, N-CH3). 13C NMR: δ 159.1, 145.6, 145.2, 117.4, 111.6, 61.3, 33.1. |
With pyridine; In dichloromethane; at 20℃; for 1h;Inert atmosphere; | General procedure: In a 50 mL round bottom flask, equipped witha magnetic stir bar and a septum, air was displaced with a continuous nitrogenflow. Then, in approximately 10 mL of dichloromethane, 1 mmol of the appropriateacylchloride and 1.1 mmol of N,O-dimethylhydroxylamine hydrochloride weredissolved and injected into the flask using a syringe . The reaction mixturewas cooled to 0C, followed by the addition of 2.2 mmol of pyridine. The resultingmixture was stirred at ambient temperature for an hour. This mixture was then partitionedbetween brine and a 1:1 mixture of ether and dichloromethane to separate theorganic layer from the aqueous layer via separation funnel. The organic layerwas dried with sodium sulfate, and filtered into an oven dried round bottomflask, using a Buchner funnel under vacuum. The solvent of the organic layerwas then removed, using a rotary evaporator, to isolate the amide product.Structure and purity were characterized by 1H NMR. | |
In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of in situ generated CPI-Cl (generated by the treatment of 2,3 diphenylcyclopropenone (1.1 mmol) with oxalyl chloride (1 mmol) in Cl2Cl2) was added aryl/heterocyclic/Nα-protected amino acid (1 mmol), DIPEA (2 mmol) stirring at room temperature. After the formation of acid chloride solution of N,O-dimethylhydroxylamine (2 mmol) in CH 2 Cl 2 was added. After the completion of the reaction (determined by TLC), solvent was evaporated under vacuo and diluted with EtOAc, washed with 5% citric acid (10 mL x 2) and Na 2 CO 3 (10 mL x 2), water, brine and dried over anhydrous Na 2 SO 4 . After filteration, solvent was evaporated and purified by column chromatography using hexane and EtOAc as eluents. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | General procedure: To a solution of acid 1 (1.0g, 8.9 mmol) in THF (15 mL) was added Et3N (3.1 mL, 22.2 mmol), and T3P (50% solution in EtOAc, 10.6mL, 17.7 mmol) at 0-5 C and the solution was stirred for about 10 min under a nitrogen atmosphere. Then N,O-dimethylhydroxylaminehydrochloride salt (1.1g, 13.3 mmol) was added to the reaction mixture at 0-5 C and the heterogeneous mixture was allowed to stir at room temperature till the completion of the reactionas indicated by TLC (see Table S-1). The mixture was then diluted with water(20 mL) followed by ethyl acetate (20 mL) and stirred for about 10 min. The separated organic layer was collected, washed with 5% citric acid (2 x10 mL),5% Na2CO3 (2 x 10 mL), and then brine solution. The collected organic layer was dried over anhydrous Na2SO4, filtered and concentrated under low vacuum. The crude product obtainedwas purified by flash column chromatography over silicagel (100-200 mesh) using 12-15% EtOAc / n-hexane as eluent to affordthe desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine; In dichloromethane; at 20℃; for 2h;Inert atmosphere; | General procedure: To a stirred solution of acid (1 equiv) in CH2Cl2 (for a solution of0.1 mol L1) were added oxalyl chloride [(COCl)2; 1.25 equiv] and DMF (0.004 equiv) at room temperature. After 1.5 h, the solventand the excess oxalyl chloride were removed by evaporation under vacuum. CH2Cl2 (for a solution of 0.1 mol L1), N,O-dimethylhydroxylamine (1.4 equiv), and Et3N (3 equiv) were then successively added at room temperature. After 2 h, the reaction was quenched at room temperature with a saturated solution of NaHCO3 and the mixture extracted twice with CH2Cl2. The combined organic layers were then washed with a saturated solution of NH4Cl and brine. The organic layer was then dried with anhydrous MgSO4, filtered, and concentrated under vacuum to afford the crude Weinreb amine.To a stirred solution of diisopropylamine (DIPA; 3 equiv) in THF (for a solution of 0.1 mol L1) was added n-Butyl lithium (nBuLi,1.2 M in hexane, 3.1 equiv) at -78 C. After 30 min at 0 C, the medium was recooled to -78 C and freshly distilled tBu acetate (3 equiv) was added. After 30 min at -78 C, crude Weinreb amide (1 equiv) was added at this temperature. After 1 h, the reaction was quenched at room temperature with a saturated solution of NaHCO3 and the mixture extracted twice with EtOAc. The combined organic layers were then washed with a saturated solution of NH4Cl. The organic layer was then dried with anhydrous MgSO4, filtered, and concentrated under vacuum to afford the crude tert-butyl ester. To a stirred solution of tert-butyl ester (1 equiv) in acetone (10 equiv) were added acetic anhydride (15 equiv) and sulfuric acid (1 equiv) at 0 C. The medium was then warmed slowly to room temperature over 10 min. After 45 min, the reaction was quenched at room temperature with an aqueous solution containing sodium carbonate (30 equiv) and EtOAc (100 mL) was added.The biphasic medium was then stirred for 40 min (hydrolysis ofthe remaining acetic anhydride) and the aqueous layer was extracted twice with EtOAc. The combined organic layers were then washed with a saturated solution of NH4Cl. The organic layer was dried with anhydrous MgSO4, filtered and concentrated under vacuum. The crude residue was finally purified by flash chromatography silica gel using an appropriate gradient of a cyclohexane/EtOAc mixture as eluent to give the desired dioxinone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium metal trapped in the nanoscale pores of silica gel; In tetrahydrofuran; for 4h;Glovebox; Sealed tube; Inert atmosphere; Reflux; | General procedure: In a helium-filled glove box, the desired number ofequivalents of Na-AG or Na-SG were added to a round bottom flask, along with aglass-coated stir bar, and the flask sealed with a septum. This closed systemwas then taken out of the glove box, continuously purged with nitrogen, followedby injection of the pure synthesized Weinreb amide dissolved in THF. The resulting mixture was stirred for thetime specified. After completion of the reaction, the mixture was then partitioned using ethyl acetate and brine. The organic layer was concentrated under reducedpressure using a rotary evaporator. 1H NMR of the crude product wastaken to check for reaction extent/completion and to identify the productsobtained. Crude product was fractionated and purified by columnchromatography on silica gel to afford the desired product and byproducts. |
43% | With 3C12H16O8S2(2-)*6Na(1+)*C58H42N2; triethylamine; In water; at 20℃; for 5h;Irradiation; | General procedure: A 4 mL sample bottle was charged with 4 (0.13 mmol), triethylamine (26.3 mg, 0.26 mmol, 2.0 equiv.),and a H2O solution of 3c (ca. 1.3 mM, 2 mL, 2 mol%), and then it was placed at a distance of 1 cmaway from blue LED lamps (λ= 425 nm). The mixture was irradiated with stirring and cooling by afan for 3-48 h. Then, 5 mL H2O was added, and the resulting mixture was extracted with 15 mL ofCH2Cl2 ×3. The organic layer was dried over Na2SO4 and evaporated. Crude product was purified byGPC. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | To a stirred solution of (2R,6S)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)- 2,6-dimethylmorpholine (Intermediate 3, 1 g, 2.02 mmol) in THF (8 mL) was added sBuLi (1.3 M in cyclohexane/hexanes, 3.1 ml, 4.03 mmol) at -70C under nitrogen atmosphere. After stirring for 1 h at this temperature, <strong>[95091-92-2]N-methoxy-N-methylfuran-2-carboxamide</strong> (0.939 g, 6.05 mmol) was added in 3 ml of THF. After stirring for 11A h at -70C, the reaction quenched with sat. ammonium chloride solution and the aqueous layer extracted by ethyl acetate (2 X 100 mL). The organic phases were combined, dried (Na2SO4), and concentrated. The residue purified over a silica gel flash column using a gradient of ethyl acetate in hexanes to give the title compound (0.90 g, 76 %). MS (ES) MH+: 590 for C34H37F2NO4Si1H NMR (300 MHz, CDCl3) δ: 1.05 (s, 9H), 1.08 (d, 6H), 2.59-2.93 (m, 4H), 3.35-3.58 (m, 2H), 4.71 (s, 2H), 6.58 (dd,1H), 7.18 (d, 1H), 7.32-7.48 (m, 6H), 7.57-7.74 (m, 6H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.8% | Magnesium turnings (21.6 g, 0.901 mol, 3.7 eq/halide) were covered with anhydrous Et2O (150 mL) and a solution of 1-bromoundecane (54.0 mL, 0.242 mol) in anhydrous Et2O (200 mL) was added in small aliquots until the reaction begins. The remaining bromoundecane solution was added dropwise, then heated to reflux (1 hour), allowed to cool to rt and then added to a cooled solution of the Weinreb amide (30.0 g, 0.194 mol in 200 mL anhydrous Et2O, 0 C.) via cannula. The resulting slurry was stirred (3 h) and then quenched with equal amounts of 1 N HCl and H2O. After warming to rt the mixture was separated and the aqueous layer was extracted with Et2O (2×). The combined organics were washed with sat'd. NaHCO3, brine, dried (Na2SO4), filtered, and evaporated to yield crude furyl ketone, which was distilled under vacuum (b.p. 131-138 C., 0.2 mm Hg) to give pure furyl ketone (40.2 g, 0.161 mol, Yld. 82.8%). 1H NMR: δ 7.55 (m, 1H, H-2), 7.15 (d, 1H, 3JH,H=3.6 Hz, H-4), 6.50 (dd, 1H, 3JH,H=1.7 Hz, 3JH,H=3.6 Hz, H-3), 2.78 (t, 2H, 3JH,H=7.5 Hz, H-7), 1.69 (quintet, 2H, 3JH,H=7.4 Hz, H-8), 1.34-1.23 (m, 16H), 0.90 (t, 3H, 3JH,H=7.1, CH3). 13C NMR: δ 190.1, 153.3, 146.5, 117.1, 112.5, 38.9, 32.3, 30.1, 30.0, 29.9, 29.8, 29.7, 24.7, 23.0, 14.5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82.3% | Magnesium turnings (1.50 g, 62.5 mmol) were covered with anhydrous Et2O (20 mL) and a solution of 1-bromopentane (2.0 mL, 16.2 mmol) in anhydrous Et2O (16 mL) was added in small aliquots until the reaction begins. The remaining bromopentane solution was added dropwise, then heated to reflux (1 hour), allowed to cool to rt and then added to a cooled solution of the Weinreb amide (1.65 g, 10.6 mmol in 20 mL anhydrous Et2O, 0 C.) via cannula. The resulting slurry was stirred (3 h) and then quenched with equal amounts of 1 N HCl and H2O. After warming to rt the mixture was separated and the aqueous layer was extracted with Et2O (2×). The combined organics were washed with sat'd. NaHCO3, brine, dried (Na2SO4), filtered, and evaporated to yield crude furyl ketone, which was distilled under vacuum (b.p. 73-74 C., 0.2 mm Hg) to give pure furyl ketone (1.45 g, 8.72 mmol, Yld. 82.3%). 1H NMR: δ 7.57 (dd, 1H, 3JH,H=1.6 Hz, 4JH,H=0.76 Hz, H-2), 7.17 (dd, 1H, 3JH,H=3.5 Hz, 4JH,H=0.74 Hz, H-4), 6.52 (dd, 1H, 3JH,H=1.6 Hz, 3JH,H=3.5 Hz, H-3), 2.80 (t, 2H, 3JH,H=7.4 Hz, H-7), 1.71 (quintet, 2H, 3JH,H=7.4 Hz, H-8), 1.33 (m, 4H, H-9, H-10), 0.90 (t, 3H, 3JH,H=7.0, H-11). 13C NMR: δ 190.3, 153.2, 146.6, 117.2, 112.5, 38.9, 31.9, 24.4, 22.9, 14.3. DEP/CI/MS: m/z 167 [M+H]+, Elemental Analysis: Calcd for C10H14O2: C, 72.26; H, 8.49; O, 19.25. Found: C, 71.50; H, 8.70; O, 19.81. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Magnesium turnings (8.20 g, 0.342 mol, 4.5 eq/halide) were covered with anhydrous THF (40 mL) and a solution of 1-(tetrahydropyran-2-yloxy)-6-hexyl bromide (20.1 g, 76.0 mmol in anhydrous 100 mL THF) was added dropwise once the reaction was initiated with 1,2-dibromoethane. The remaining halide solution was added dropwise and the mixture was allowed to stir at rt overnight. The resulting mixture was then added to a cooled solution of the Weinreb amide (10.3 g, 66.1 mmol in 100 mL anhydrous THF, 0 C.) via cannula. The resulting slurry was stirred (3 h) and then quenched with equal amounts of 1 N HCl and H2O. After warming to rt the mixture was separated and the aqueous layer was extracted with Et2O (2×). The combined organics were washed with sat'd. NaHCO3, brine, dried (Na2SO4), filtered, and evaporated to yield crude residue, which was then dissolved in MeOH (200 mL) with a small amount of TsOH and allowed to stir overnight. The reaction mixture was stirred with NaHCO3, evaporated, and the residue taken up in hexane. The hexane portion was washed with H2O (2×), brine, dried (Na2SO4), and concentrated to yield crude furyl ketone, which was distilled under vacuum (b.p. 164-167 C., 0.2 mm Hg) to give pure furyl ketone (6.95 g, 35.4 mmol, Yld. 53.6%). 1H NMR: δ 7.57 (dd, 1H, 3JH,H=1.7 Hz, 4JH,H=0.74 Hz, H-2), 7.17 (dd, 1H, 3JH,H=3.6 Hz, 4JH,H=0.76 Hz, H-4), 6.52 (dd, 1H, 3JH,H=3.6 Hz, 3JH,H=1.7 Hz, H-3), 3.63 (t, 2H, 3JH,H=6.6 Hz, H-12), 2.81 (t, 2H, 3JH,H=7.6 Hz, H-7), 2.13 (bs, 1H, OH), 1.72 (quintet, 2H, 3JH,H=7.4 Hz, H-8), 1.57 (quintet, 2H, 3JH,H=6.7 Hz, H-11), 1.39 (m, 4H, H-9 and 10). 13C NMR: δ 189.8, 152.7, 146.3, 117.0, 112.2, 62.8, 38.3, 32.5, 29.0, 25.5, 24.2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Magnesium turnings (2.0 g, 83.3 mmol) were covered with anhydrous Et2O (10 mL) and a solution of 1-bromoundecene (5.0 mL, 23.0 mmol) in anhydrous Et2O (15 mL) was added in small aliquots until the reaction begins. The remaining halide solution was added dropwise, then heated to reflux (1 hour), allowed to cool to rt and then added to a cooled solution of the Weinreb amide (2.82 g, 18.2 mmol in 15 mL anhydrous Et2O, 0 C.) via cannula. The resulting slurry was stirred (3 h) and then quenched with equal amounts of 1 N HCl and H2O. After warming to rt the mixture was separated and the aqueous layer was extracted with Et2O (2×). The combined organics were washed with sat'd. NaHCO3, brine, dried (Na2SO4), filtered, and evaporated to yield crude furyl ketone. 1H NMR: δ 7.58 (dd, 1H, 3JH,H=1.7 Hz, 4JH,H=0.74 Hz, H-2), 7.18 (dd, 1H, 3JH,H=3.6 Hz, 4JH,H=0.74 Hz, H-4), 6.53 (dd, 1H, 3JH,H=1.7 Hz, 3JH,H=3.6 Hz, H-3), 5.82 (m, 1H), 5.00 (m, 1H, vinyl), 4.92 (m, 1H, vinyl), 2.82 (t, 2H, 3JH,H=7.5 Hz, H-7), 2.04 (qd, 2H, 3JH,H=7.5 Hz, H-15), 1.72 (quintet, 2H, 3JH,H=7.5 Hz, H-8), 1.37-1.20 (m, 12H). 13C NMR: δ 189.9, 152.9, 146.2, 139.2, 116.8, 114.1, 112.1, 38.5, 33.8, 29.7, 29.4, 29.3, 29.2, 29.1, 28.9, 24.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
General procedure: To a stirred solution of acid (1 equiv) in CH2Cl2 (for a solution of0.1 mol L1) were added oxalyl chloride [(COCl)2; 1.25 equiv] and DMF (0.004 equiv) at room temperature. After 1.5 h, the solventand the excess oxalyl chloride were removed by evaporation under vacuum. CH2Cl2 (for a solution of 0.1 mol L1), N,O-dimethylhydroxylamine (1.4 equiv), and Et3N (3 equiv) were then successively added at room temperature. After 2 h, the reaction was quenched at room temperature with a saturated solution of NaHCO3 and the mixture extracted twice with CH2Cl2. The combined organic layers were then washed with a saturated solution of NH4Cl and brine. The organic layer was then dried with anhydrous MgSO4, filtered, and concentrated under vacuum to afford the crude Weinreb amine.To a stirred solution of diisopropylamine (DIPA; 3 equiv) in THF (for a solution of 0.1 mol L1) was added n-Butyl lithium (nBuLi,1.2 M in hexane, 3.1 equiv) at -78 C. After 30 min at 0 C, the medium was recooled to -78 C and freshly distilled tBu acetate (3 equiv) was added. After 30 min at -78 C, crude Weinreb amide (1 equiv) was added at this temperature. After 1 h, the reaction was quenched at room temperature with a saturated solution of NaHCO3 and the mixture extracted twice with EtOAc. The combined organic layers were then washed with a saturated solution of NH4Cl. The organic layer was then dried with anhydrous MgSO4, filtered, and concentrated under vacuum to afford the crude tert-butyl ester. To a stirred solution of tert-butyl ester (1 equiv) in acetone (10 equiv) were added acetic anhydride (15 equiv) and sulfuric acid (1 equiv) at 0 C. The medium was then warmed slowly to room temperature over 10 min. After 45 min, the reaction was quenched at room temperature with an aqueous solution containing sodium carbonate (30 equiv) and EtOAc (100 mL) was added.The biphasic medium was then stirred for 40 min (hydrolysis ofthe remaining acetic anhydride) and the aqueous layer was extracted twice with EtOAc. The combined organic layers were then washed with a saturated solution of NH4Cl. The organic layer was dried with anhydrous MgSO4, filtered and concentrated under vacuum. The crude residue was finally purified by flash chromatography silica gel using an appropriate gradient of a cyclohexane/EtOAc mixture as eluent to give the desired dioxinone. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | General procedure: A solution of NHMe(OMe) (0.360 g, 6.0 mmol) and benzoic acid (0.244 g, 2.0 mmol) was stirred in dry toluene (10 mL) at 0 C for 10 min. A solution of PCl3 (0.137 g, 1.0 mmol) in dry toluene (2 mL) was then added dropwise to the mixture. The mixture was warmed to r.t. slowly and then stirred at 60 C for 0.5 h. When the reaction was complete (TLC monitoring), the mixture was cooled to r.t. The mixture was then quenched with sat. NaHCO3 soln (20 mL) and extracted with EtOAc (3 × 10 mL). The combined organic layers were dried (anhyd MgSO4). The solvent was removed in vacuo.The product was purified by column chromatography (silica gel, petroleum ether-EtOAc, 3:2) to give pure 3a as a colorless oil; yield: 320 mg (97%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
> 99%Chromat. | With lithium diisobutyl-tert-butoxyaluminum hydride; In tetrahydrofuran; hexane; at 0℃;Inert atmosphere; | General procedure: The following experimental procedure for the partial reduction of N-methoxy-N-methylbenzamide to benzaldehyde is representative. A dry, argon-flushed flask, equipped with a magnetic stirring bar and a septum, was charged with N-methoxy-N-methylbenzamide (0.08 mL, 0.5 mmol) and THF (5 mL). After cooling to 0 C, LDBBA (1.38 mL, 0.4M 0.55 mmol) was added dropwise and the mixture was stirred for 30 min at the same temperature. The reaction was quenched with 1N aqueous HCl (5 mL) and the product was extracted with diethyl ether (10 mL). The organic layer was dried over anhydrous magnesium sulfate. GC analysis showed quantitative conversion to benzaldehyde. All products in Table 2 were confirmed through a comparison with the GC data of an authentic sample. |
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