Structure of 25021-04-9
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CAS No. : | 25021-04-9 |
Formula : | C6H8O2 |
M.W : | 112.13 |
SMILES Code : | O=C(O)/C=C1CCC/1 |
MDL No. : | MFCD09865731 |
InChI Key : | ACWUGSRELMTOFJ-UHFFFAOYSA-N |
Pubchem ID : | 21923173 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P280-P301+P312-P302+P352-P305+P351+P338 |
* 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 |
---|---|---|
62% | With lithium hydroxide monohydrate; water; In tetrahydrofuran; methanol; at 20℃; for 16h; | In 1:1:0.5 THF/water/Methanol (10:10:5 mL each), <strong>[27741-65-7]ethyl 2-cyclobutylideneacetate</strong> (1.2 g, 8.57 mmol) and lithium hydroxide monohydrate (2.15 g, 51.4 mmol) was added at room temperature. Reaction mixture was allowed to stir at room temperature for 16 h. TLC showed absence of starting material (Rf=0.4, 30% ethyl acetate/n-hexane). THF and Methanol was removed under reduced pressure. Aqueous layer was acidified with citric acid and extracted with ethyl acetate. Crude product was purified by column chromatography (silica gel 60-120 mesh ethyl acetate/n-hexane as eluent) to afford white solid. [0505] Yield: 0.6 g (62%) [0506] 1H NMR (400 MHz, CDCl3): delta 2.02-2.20 (m, 2H). 2.86 (t, J=7.8 Hz, 2H), 3.14 (t, J=7.8 Hz, 2H), 5.59 (t, J=2 Hz, 1H). |
62% | With water; sodium hydroxide; In ethanol; at 27℃; for 12h; | To a solution of 25% NaOH in H20 (1.5 mL) and EtOH (1.5 mL) was added <strong>[27741-65-7]ethyl 2-cyclobutylideneacetate</strong> 76 (0.20 g, 1.42 mmol) and stirred for 12h at room temperature, reaction mixture was concentrated to one third and acidified with iN HC1 to pH 2-3 and extracted with ethyl acetate (2 x 50 mL), organic layer was washed with water, dried over Na2SO4 and concentrated to obtain pure compound 2- cyclobutylideneacetic acid precursor-44 as off white solid (0.10 g, 62% Yield). 1IETNMR (400 MHz, CDC13): oe 5.59 (t, 111), 3.14 (t, 2H), 2.86 (t, 2H), 2.13-2.05 (m, 2H). |
54% | With lithium hydroxide; In tetrahydrofuran; water; at 20℃; for 18h; | A solution of LiOH · H2O (4.20 g, 100 mmol) in water (25 mL) was added to a solution of raw221 ethyl cyclobutylidenacetat (1.40 g, 10 mmol) in THF (25 mL). The mixture was stirred for 18 h at room222 temperature. TLC showed very little conversion. THF, water and MeOH (10 mL each), were added223 and the mixture was stirred for further three days. No starting material was visible in TLC. The224 mixture was concentrated under reduced pressure to about 30 mL, washed with ether (2 x 10 mL),225 acidified with conc. HCl (ca. 8 mL) and extracted with Et2O (3 x 10 mL). This extract was dried over226 anhydrous Na2SO4 and evaporated. 580 mg of the raw product (0.99 g) were purified by CC (silica,227 cyclohexane / EtOAc = 3:1 to 2:1) resulting in 352 mg cyclobutylideneacetic acid (2a) (54%). |
51% | With potassium hydroxide; In methanol; water; at 20℃; for 16h; | (0203) Triethyl phosphonoacetate (3.32 g, 1.0 equiv) was dissolved in abs. tetrahydrofuran and added to a suspension, cooled down to 0 C., of sodium hydride (0.58 g, 1.02 equiv, 60% dispersion) in abs. tetrahydrofuran (5 mL). The resulting reaction mixture was stirred at a temperature of 0 C. for 10 minutes and then admixed with a solution of cyclobutanone (1.0 g, 1.0 equiv) in abs. tetrahydrofuran (5 mL), and the mixture was stirred at room temperature for a further 4 h. After the cautious addition of water, the reaction mixture was concentrated under reduced pressure and admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), <strong>[27741-65-7]ethyl cyclobutylideneacetate</strong> (1.5 g, 75% of theory) was isolated. Ethyl cyclobutylideneacetate (1.0 g, 1.0 equiv) was dissolved in methanol and admixed with a 1 M solution of KOH in aq. methanol. The resulting reaction mixture was stirred at room temperature for 16 h, then neutralized with dil. HCl, admixed with water, concentrated under reduced pressure and then admixed with dichloromethane. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), cyclobutylideneacetic acid (0.40 g, 51% of theory) was isolated. Aniline (0.26 g, 1 equiv.) was dissolved in dichloromethane (5 mL) and cooled down to a temperature of 0 C., and diisopropylethylamine (1.98 mL, 4.0 equiv.), cyclopentylideneacetic acid (0.30 g, 1.0 equiv.) and N,N,N?,N?-tetramethyl-O-(benzotriazol-1-yl)uronium tetrafluoroborate (0.97 g, 1.1 equiv.) were added. The resulting reaction mixture was stirred at room temperature for 3 h, and water and dichloromethane were then added. The aqueous phase was then repeatedly extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 2-cyclobutylidene-N-phenylacetamide (0.27 g, 54% of theory) was isolated. In the next step, aluminum trichloride (0.42 g, 3.0 equiv.) was initially charged in abs. dichloroethane (5 mL) under argon in a baked-out round-bottom flask and then, while cooling with ice, a solution of 2-cyclobutylidene-N-phenylacetamide (0.20 g, 1.0 equiv.) in abs. dichloroethane (5 mL) was added. The resulting reaction mixture was stirred at room temperature for a further 4 h and then added cautiously to ice-water. After adding aqueous HCl and dichloromethane, the aqueous phase was extracted repeatedly with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered and concentrated cautiously under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1?H-spiro[cyclobutyl-1,4?-quinolin]-2?(3?H)-one was isolated as a colorless solid. 1?H-Spiro[cyclobutyl-1,4?-quinolin]-2?(3?H)-one (0.2 g, 1 equiv.) was added to conc. acetic acid (1.5 mL) and then cautiously admixed at 0 C. with fuming nitric acid (0.5 mL). The resulting reaction mixture was then stirred at 90 C. for 2 h and, after cooling to room temperature, cautiously diluted with ice-water. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 6?-nitro-1?H-spiro[cyclobutyl-1,4?-quinolin]-2?(3?H)-one (100 mg, 78% of theory) was isolated as a colorless solid. 6?-Nitro-1?H-spiro[cyclobutyl-1,4?-quinolin]-2?(3?H)-one (100 mg, 1.0 equiv.) was dissolved under argon in abs. dioxane (2 mL) and admixed with fine cesium carbonate powder (400 mg, 3.0 equiv.). After stirring at room temperature for 5 min, cyclobutylmethyl bromide (110 mg, 2.0 equiv.) and potassium iodide (35 mg, 0.1 equiv.) were added at room temperature. The resulting reaction mixture was stirred at 150 C. under microwave conditions for 1 h and, after cooling to room temperature, water and ethyl acetate were added. The aqueous phase was then repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. By column chromatography purification of the crude product obtained (ethyl acetate/heptane gradient), 1-(cyclopropylmethyl)-6?-nitro-1?H-spiro[cyclobutyl-1,4?-quinolin]-2?(3?H)-one (70 mg, 60% of theory) was isolated as a colorless solid. In the next step, 1-(cyclopropylmethyl)-6?-nitro-1?H-spiro[cyclo... |
Step 1: Cyclobutylideneacetic acid To a solution of <strong>[27741-65-7]ethyl 2-cyclobutylideneacetate</strong> (5.5 g) in 40 mL EtOH was added an aqueous NaOH solution (10 g NaOH in 40 mL H2O). The mixture was stirred at room temperature overnight. The volume of the reaction mixture was reduced to one third and the pH was modified to 2-3. The solid present was collected by filtration and dried under high vacuum, giving the pure cyclobutylideneacetic acid as an off-white solid (3.5 g) 1H-NMR (300 MHz, CDCl3) delta=5.57 (s, 1H); 4.13 (q, J=7.05 Hz, 2H); 3.11 (m, 2H); 2.81 (m, 2H); 2.08 (m, 2H); 1.26 (t, J=6.97 Hz) ppm. MS: (m/z)=113 (100, M+H)+. |
Tags: 25021-04-9 synthesis path| 25021-04-9 SDS| 25021-04-9 COA| 25021-04-9 purity| 25021-04-9 application| 25021-04-9 NMR| 25021-04-9 COA| 25021-04-9 structure
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