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CAS No. : | 50820-65-0 | MDL No. : | MFCD00211063 |
Formula : | C10H9NO2 | Boiling Point : | No data available |
Linear Structure Formula : | - | InChI Key : | AYYOZKHMSABVRP-UHFFFAOYSA-N |
M.W : | 175.18 | Pubchem ID : | 639844 |
Synonyms : |
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Signal Word: | Warning | Class: | |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | |
Hazard Statements: | H315-H319-H335 | Packing Group: | |
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 |
---|---|---|
95% | With lithium hydroxide monohydrate; In tetrahydrofuran; methanol; water; | (c) A solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (11.0 g) in a mixture of tetrahydrofuran (150 ml), methanol (150 ml), and water (63 ml) was treated with lithium hydroxide monohydrate (15.8 g). The mixture was stirred at 60 C. for 6 hours and then concentrated to remove the organic solvents. The residue was dissolved in water, and the solution was acidified with 50% (v/v) hydrochloric acid. The precipitate which formed was collected by filtration and dried to give indole-6-carboxylic acid (9.6 g, 95%) as a tan powder; mp 253-254: NMR (80 MHz; CDCl3) 6.51(m, 1H, H3 -indole), 8.04(m, 1H, H7 -indole), 11.43(broad s, 1H, NH), 12.42(broad s, 1H, OH). |
95% | With lithium hydroxide monohydrate; In tetrahydrofuran; methanol; water; | (c) A solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (11.0 g) in a mixture of tetrahydrofuran (150 ml), methanol (150 ml), and water (63 ml) was treated with lithium hydroxide monohydrate (15.8 g). The mixture was stirred at 60C for 6 hours and then concentrated to remove the organic solvents. The residue was dissolved in water, and the solution was acidified with 50% (v/v) hydrochloric acid. The precipitate which formed was collect by filtration and dried to give indole-6-carboxylic acid (9.6 g, 95%) as a tan powder; mp 253-254; NMR (80 MHz; CDCl3): 6.51(m, 1H, H3-indole), 8.04(m, 1H, H7-indole), 11.43(broad s, 1H, NH), 12.42(broad s, 1H, OH). |
88% | Step 1: Lithium hydroxide (0.72 g, 17.2 mmol, 3 equiv.) in water (10 mL) was added to <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (1 g, 5.7 mmol, 1 equiv.) in tetrahydrofuran (10 mL) and the mixture stirred at 80 C. for 16 hours. The solution was concentrated under vacuum then diluted with dichloromethane (10 mL) and the organic layer extracted with water (3×10 mL). The aqueous phase was acidified to pH<1 with concentrated HCl forming a precipitate. The precipitate was filtered and washed with 1 M aqueous HCl (3×10 mL) to afford 1H-indole-6-carboxylic acid as a white solid, 0.807 g (88% yield). LC (at)215 nm; Rt 1.02: 100%, m/z (ES+): 162 (M+H+.); δH (400 MHz; MeOD) 8.15 (1H, d), 7.72 (1H, m), 7.67 (1H, m), 7.45 (1H, m), 6.53 (1H, m). |
85% | To a solution of <strong>[50820-65-0]methyl indole-6-carboxylate</strong> (3.0 g) in MeOH (34 mL), a 3M aqueous solution of LiOH (17 mL, 3.0 equiv.) was added. The reaction mixture was heated at reflux for 1 Hr, then cooled at 0C, diluted with water (50 mL) and acidified with HCl 12M (5 mL). The mixture was extracted with AcOEt (3*30 mL). The combined organic layers were washed with brine (30 mL), dried over MgSO4 and concentrated to give the product as a yellow solid (2.3 g, 85%). M/Z (M+H)+ = 162. | |
57% | Step 4. 1H-Indole-6-carboxylic acid A solution of <strong>[50820-65-0]methyl 1H-indole-6-carboxylate</strong> (1.3 g, 7.43 mmol, 1.00 equiv) in tetrahydrofuran (20 mL) was placed into a 250-mL round-bottom flask. Then CH3OH (20 mL), H2O (10 mL), LiOH.H2O (1.9 g, 45.24 mmol, 6.09 equiv) were added. The resulting solution was stirred overnight at 60 C. The resulting mixture was concentrated in vacuo, and diluted with water. The resulting solution was extracted with 2*100 mL of ether and the aqueous layers were combined. The pH value of the solution was adjusted to pH 3 with hydrochloric acid, and the solids were collected by filtration. This resulted in 0.68 g (57%) of 1H-indole-6-carboxylic acid as a light yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | In tetrahydrofuran; palladium; ethyl acetate; | b. Methyl indole-6-carboxylate A solution of methyl E-4-(2-dimethylaminovinyl)-3-nitrobenzoate (5.58 g) in tetrahydrofuran (100 ml) was hydrogenated at 3.45 bar in the presence of 10% (w/w) palladium on carbon (1.1 g) for 35 min. The catalyst was removed by filtration through diatomaceous earth and the filtrate was evaporated. The residue was dissolved in ethyl acetate and the solution obtained was washed successively with 10% (v/v) hydrochloric acid, water, and brine; then dried (MgSO4) and evaporated to give methyl indole-6-carboxylate (3.32 g, 85%) as a white solid; NMR (80 MHz, CDCl3): 3.92(s, 3H, OCH3), 6.57(m, 1H, H3 -indole), 7.32(t, 1H, H2 -indole), 7.10(d, 1H, H4 -indole), 7.87(dd, 1H, H5 -indole), 8.16(broad s, 1H, H7 -indole). |
85% | In tetrahydrofuran; palladium; ethyl acetate; | (b) A solution of methyl E-4-(2-dimethylaminovinyl)-3-nitrobenzoate (5.58 g) in tetrahydrofuran (100 ml) was hydrogenated at 3.45 bar in the presence of 10% (w/w) palladium on carbon (1.1 g) for 35 minutes. The catalyst was removed by filtration through diatomaceous earth and the filtrate was evaporated. The residue was dissolved in ethyl acetate and the solution obtained was washed successively with 10% (v/v) hydrochloric acid, water, and brine, then dried (MgSO4) and evaporated to give methyl indole-6-carboxylate (3.32 g, 85%) as a white solid; NMR (80 MHz, CDCl3) 3.92(s, 3H, OCH3), 6.57(m, 1H, H3 -indole), 7.32(t, 1H, H2 -indole), 7.10(d, 1H, H4 -indole), 7.87(dd, 1H, H5 -indole), 8.16(broad s, 1H, H7 -indole). |
85% | In tetrahydrofuran; palladium; ethyl acetate; | (b) A solution of methyl E-4-(2-dimethylaminovinyl)-3-nitrobenzoate (5.58 g) in tetrahydro-furan (100 ml) was hydrogenated at 3.45 bar in the presence of 10% (w/w) palladium on carbon (1.1 g) for 35 minutes. The catalyst was removed by filtration through diatomaceous earth and the filtrate was evaporated. The residue was dissolved in ethyl acetate and the solution obtained was washed successively with 10% (v/v) hydrochloric acid, water, and brine, then dried (MgSO4) and evaporated to give methyl indole-6-carboxylate (3.32 g, 85%) as a white solid; NMR (80 MHz, CDCl3): 3.92(s, 3H, OCH3), 6.57(m, 1H, H3-indole), 7.32(t, 1H, H2-indole), 7.10(d, 1H, H4-indole), 7.87(dd, 1H, H5-indole), 8.16(broad s, 1H, H7-indole). |
84% | With hydrogen;palladium on activated charcoal; In tetrahydrofuran; at 20℃; | Step 3. Methyl 1H-indole-6-carboxylate A solution of (E)-methyl 4-(2-(dimethylamino)vinyl)-3-nitrobenzoate (2.2 g, 8.80 mmol, 1.00 equiv) in tetrahydrofuran (50 mL) was placed into a 100-mL round-bottom flask. Then 2.4 g of palladium on carbon was added. An atmosphere of hydrogen gas was placed over the contents of the flask, and the reaction was stirred overnight at room temperature. Then the solids were filtered off, and the resulting mixture was concentrated in vacuo. This resulted in 1.3 g (84%) of methyl 1H-indole-6-carboxylate as brown oil. |
With sodium dithionite; In tetrahydrofuran; ethanol; water; | Production Example 5 6-methoxycarbonylindole To a mixed solvent of tetrahydrofuran (30 ml), ethanol (30 ml) and water (100 ml), added are methyl E-4-(2-dimethylaminovinyl)-3-nitrobenzoate (10.0 g) and sodium hydrosulfite (104.5 g), and stirred at 70 C. for 1 hours. After this is cooled to room temperature, a saturated saline solution is added thereto. Then, this is extracted with chloroform. The organic layer is dried, and the solvent is evaporated away. The resulting residue is purified through silica gel column chromatography (eluent: hexane/ethyl acetate=2/1 to 1/1) to obtain 6-methoxycarbonylindole (2.79 g). 1H-NMR (CDCl3, δ): 3.93 (3H, s), 6.60 (1H, s), 7.37 (1H, m), 7.66 (1H, d, J=8.3 Hz), 7.81 (1H, dd, J=1.3 and 8.3 Hz), 8.17 (1H, s), 8.52 (1H, brs). | |
palladium-carbon; In tetrahydrofuran; | EXAMPLE 1 Methyl 6-indolecarboxylate STR8 16.7 g (0.060 mol) of methyl 4-(2-dimethylaminoethenyl)-3-nitrobenzoate [prepared according to the general working procedure of L. F. Tietze and Th. Eicher, "Reaktionen und Synthesen" (Reactions and Syntheses), p. 172, Thieme, Stuttgart 1981] were hydrogenated in 300 ml of tetrahydrofuran containing 1.1 g of palladium carbon (10%). The solution was filtered for 2 hours through kieselguhr and the catalyst was washed with 50 ml of tetrahydrofuran. The solvent was removed in vacuo. In order to remove a small amount of impurity (methyl 3-amino-4-methylbenzoate), the product was washed successively with 10% strength hydrochloric acid, water and concentrated sodium chloride solution, dried over magnesium sulphate and concentrated on a rotary evaporator. Yield: 9.9 g (94% of theory) of yellow crystals Rf (CH2 Cl2)=0.38 Rf (CH2 Cl2, 5% MeOH)=0.53 |
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