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CAS No. : | 441715-93-1 | MDL No. : | MFCD07790764 |
Formula : | C10H8FNO | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | IQKABDVTBNOGEW-UHFFFAOYSA-N |
M.W : | 177.18 | Pubchem ID : | 6498197 |
Synonyms : |
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Signal Word: | Danger | Class: | 8 |
Precautionary Statements: | P264-P270-P280-P301+P312+P330-P305+P351+P338+P310-P501 | UN#: | 1759 |
Hazard Statements: | H318-H302 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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 |
---|---|---|
93% | With iodobenzene diacetic acid; In ethanol; | (Step 3) Synthesis of methyl (2-(6-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl)acetic acid In ethanol (15 ml), <strong>[441715-93-1]6-fluoro-1-methylindole-3-carbaldehyde</strong> (500 mg, 2.82 mmol) and methyl 4-amino-3-hydroxyphenylacetate (767 mg, 4.23 mmol) were stirred at room temperature for 2 hours. Iodobenzene diacetate (1.09 g, 3.38 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then distilled under reduced pressure to remove the solvent. The residue was purified chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1, v/v) eluate fractions, methyl (2-(6-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl)acetate (889 mg, 93%) was obtained as a brown solid. 1H-NMR (CDCl3) delta: 3.72 (s, 3H), 3.76 (s, 2H), 3.85 (s, 3H) 7.05-7.12 (m, 2H), 7.22 (dd, J=8.1,1.5Hz, 1H), 7.49 (d, J=1.5Hz, 1H), 7.65 (d, J=8.1Hz, 1H), 7.89 (s, 1H), 8.38 (dd, J=8.9,5.4Hz, 1H). MS (ESI) m/z 339 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With potassium permanganate; In acetone; | (Step 1) Synthesis of 6-fluoro-1-methylindole-3-carboxylic acid In acetone (200 ml) was dissolved <strong>[441715-93-1]6-fluoro-1-methylindole-3-carbaldehyde</strong> (3.10 g, 17.5 mmol). To the resulting solution was added potassium permanganate (0.2M aqueous solution, 175 ml, 35.0 mmol) in portions under stirring at room temperature. After stirring at room temperature for 10 hours, the reaction mixture was filtered through Celite. After the filtrate was distilled under reduced pressure under reduced pressure, the residue was acidified with 1N HCl. The crystals thus precipitated were collected by filtration under reduced pressure, washed with water, and dried under reduced pressure to give 6-fluoro-1-methylindole-3-carboxylic acid (2.37 g, 70%) as a brown solid. 1H-NMR (DMSO-d6) delta: 3.82 (s, 3H), 7.05 (m, 1H), 7.41 (d, J=9.8Hz, 1H), 7.98 (dd, J=8.6, 5.6Hz, 1H), 8.04 (s, 1H), 12.03 (s, 1H). MS (ESI) m/z 194 (M++1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | With sodium hydroxide; trichlorophosphate; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethyl acetate; N,N-dimethyl-formamide; | (Step 2) Synthesis of 6-fluoro-1-methylindole-3-carbaldehyde Phosphoryl chloride (5.87 ml, 63.0 mmol) was added in portions while stirring DMF (45 ml) at 0ØC. After stirring at the same temperature for 20 minutes, the reaction mixture was added with a solution of 6-fluoro-1-methylindole (6.71 g, 45.0 mmol) in DMF (45 ml) at 0ØC. The reaction mixture was stirred for further.5 hour. Ice water and 1N NaOH were added to the reaction mixture to neutralize the same, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from ethyl acetate eluate fractions, 6-fluoro-1-methylindole-3-carbaldehyde (4.18 g, 52%) was obtained as a colorless solid. 1H-NMR (CDCl3) delta: 3.85 (s, 3H), 7.03-7.11 (m, 2H), 7.68 (s, 1H), 8.25 (dd, 3=8.8,5.6Hz, 1H), 9.97 (s, 1H). MS (ESI) m/z 219 (M++1+CH3CN). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52% | General procedure: POCl3 (5.87 ml, 63.0 mmol) was added dropwise to DMF (45 ml) at 0 C, and the mixture was stirred for 20 min at same temperature. A solution of 6-fluoro-1-methylindole (6.71 g, 45.0 mmol) in DMF (45 ml) was added slowly to the mixture at 0 C. After being stirred at room temperature for 1.5 h, the reaction mixture was poured into ice, and the resulting mixture was neutralized with 1 N NaOH and extracted with EtOAc. The extract was washed with brine, dried over MgSO4, and concentrated to dryness. The residue was purified by column chromatography on silica gel with EtOAc as eluent to give the title compound (4.18 g, 52%) as a colorless solid. | |
General procedure: To a cooled solution of DMF (5 mL, 3 mL per 1 mL of POCl3) at 0 C was added phosphorus oxychloride (1.6 mL, 18 mmol) drop-wise, and then the mixture was stirred at the same temperature for 1 h. Then N-methyl indole (ca. 12 mmol) was added as a DMF solution (10 mL), forming a heavy suspension that required vigorous stirring. The mixture was then allowed to warm to room temperature and stirred for 5 hours. Then 2M NaOH (27 mL) was added slowly with vigorous stirring. The mixture was heated to reflux for 20 minutes. Then the reaction was cooled to room temperature and diluted with EtOAc (15 mL) and water (15 mL). The organic layer was separated and the aqueous layer was extracted with EtOAc (2×15 mL). The combined organic layers were washed with water (4×15 mL) and brine, dried over anhydrous Na2SO4 and concentrated in vacuo to furnish the desired aldehyde as yellowish solid that required no further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | General procedure: A mixture of <strong>[441715-93-1]6-fluoro-1-methylindole-3-carbaldehyde</strong> (13a) (500 mg, 2.82 mmol) and methyl 4-amino-3-hydroxyphenylacetate (11a) (767 mg, 4.23 mmol) in EtOH (15 ml) was stirred for 22 h, and iodobenzene diacetate (1.09 g, 3.38 mmol) was added portionwise to the mixture. After being stirred for 1 h, the mixture was concentrated, and the residue was purified column chromatography with n-hexane-AcOEt (1:1, v/v) as eluent to give methyl [2-(6-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl]acetate (889 mg, 93%) as a brown solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With water; iodine; oxygen; sodium carbonate; In 1,4-dioxane; at 100℃; under 760.051 Torr; for 38h;Schlenk technique; Sealed tube; | General procedure: Under air, a 20 mL of Schlenk tube equipped with a stir bar was charged with indole 1 (0.2 mmol, 1 equiv),TMEDA (75 muL, 0.5 mmol, 2.5 equiv), Na2CO3 (42.4 mg, 0.4mmol, 2.0 equiv), 1,4-dioxane (0.5 mL) and H2O (100 muL). Then I2 (101.5 mg, 0.4 mmol, 2.0 equiv) was added and the tube was sealed with a rubber plug and charged with O2. The reaction mixture was stirred at 100 C for 36 h in oil bath. After cooling to room temperature, the resultant mixture was evaporated with EtOAc (20 mL) under reduced pressure and the residue was purified by flash column chromatography on a silica gel to give the products. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium acetate; for 1h;Reflux; Inert atmosphere; | General procedure: Aldehyde (4 mmol) and ammonium acetate (12 mmol) were refluxed in nitromethane (12 mL) for 1 hour. The solvent was removed in vacuo and the residue washed with water and filtered, furnishing the desired nitro olefin as yellowish solid that required no further purification. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | General procedure: 5-Fluoroindole-3-carbaldehyde (0.5 g, 3.07 mmol) and tetrahydrofuran (10 mL) were sequentially added to a 100 mL one-neck round bottom flask, cooled to 0 C, and slowly added NaH (60%, 196 mg, 4.91 mmol) After reacting for 10 minutes,Transfer to room temperature for 1 h, add MeI (0.38 mL, 6.14 mmol),The reaction was carried out at room temperature for 15.5 h, quenched with water (5 mL), and then evaporated to ethyl ether (ethyl acetate) (ethyl acetate (40mL×1)), washed with water (20mL×3), and then ethyl acetate was collected and then purified by column chromatography ( petroleum ether) /ethyl acetate (v/v) = 5/1) to give the title compound as a white solid(0.50 g, 92%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With aluminum (III) chloride; In methanol; | General procedure: To a solution of 10 (0.5 mmol) and 1H-indole-3-carbaldehydederivatives 11 (0.5 mmol) in 2mL anhydrous methanol, AlCl3(0.05 mmol) was added then the mixture was stirred for 4-8 h in15 mL heavy-wall pressure vessel at 70C. When the completion ofreaction (TLC check), the mixture was naturally cooled to roomtemperature, and the resulting solidwas filtered. The crude productwas purified by silica gel column chromatography or recrystallizationin ethyl acetate to afford target compounds 12a-m as whitesolid with yield ranged from 56% to 75%. |
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