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Chemical Structure| 23304-48-5

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Product Details of [ 23304-48-5 ]

CAS No. :23304-48-5
Formula : C12H13NO3
M.W : 219.24
SMILES Code : COC(C=C12)=CC=C2NC=C1CC(OC)=O
MDL No. :MFCD15527683

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Application In Synthesis of [ 23304-48-5 ]

* 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.

  • Downstream synthetic route of [ 23304-48-5 ]

[ 23304-48-5 ] Synthesis Path-Downstream   1~3

  • 1
  • [ 67-56-1 ]
  • [ 3471-31-6 ]
  • [ 23304-48-5 ]
YieldReaction ConditionsOperation in experiment
85% General procedure: A reaction mixture containing the indoleacetic acid derivative (1 equivalent) and BOP-Cl (1 equivalent) in 3 mL/mmol of anhydrous CH2Cl2 is treated with triethylamine (2 equivalents) and aged at ambient temperature for 5 min. The mixture is combined with anhydrous methanol (0.14 mL/mmol) and then continuously stirred overnight at room temperature. Following dilution with dichloromethane (12 mL/mmol), the organic solution is washed with water (2x6 mL/mmol), dried over Na2SO4, and filtered. The organic filtrate is collected and concentrated in vacuo and the crude ester is purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to afford the title compound at first as viscous yellow oil, which stably crystallizes upon seeding and subsequent cold storage.#10;
85% A reaction mixture containing <strong>[3471-31-6]2-<strong>[3471-31-6](5-methoxy-1H-indol-3-yl)acetic acid</strong></strong> (0.5 g, 2.44 mmol) and BOP-CI (0.62 g, 2.44 mmol) in 7 mL of anhydrous CH2CI2 was treated with triethyl amine (0.49 g, 4.87 mmol) and allowed to stir at ambient temperature for 5 min. The mixture was then combined with anhydrous methanol (0.34 mL) and continuously stirred overnight at room temperature. Following dilution with dichloromethane (30 mL), the organic solution was washed with water (2x15 mL), dried over Na2S04, and filtered (using a commercial phase separator syringe with attached drying cartridge). The organic filtrate was collected and concentrated in vacuo and the crude ester was purified by flash chromatography on silica gel (ethyl acetate/hexane gradient) to afford the title compound as viscous yellow oil, which permanently crystallized upon storage at -20 "C (453 mg, 85percent). Ci2H 3N03, r = 219.24; 1H NMR (400 MHz, DMSO-d6) d: 3.60 (s, 3H), 3.70 (s, 2H), 3.74 (s, 3H), 6.72 (dd, J=2.4/8.8 Hz, 1 H), 6.96 (d, J=2.4 Hz, 1 H), 7.19 (d, J=2.4 Hz, 1 H), 7.23 (d, J=8.8 Hz, 1 H), 10.77 (s, 1 H); LCMS (ESI) fR: 1.95 min (>99percent, UV254), m/z: 220.1 [M+1]+.
60% With thionyl chloride; at 0 - 20℃; for 2h; A solution of 5-methoxy-3-indoleacetic acid (4) (205 mg, 1 mmol) in dry MeOH (500 mL) was cooled to 0 °C and SOCl2 (5 mmol) was added slowly. After stirring for 2 h at room temperature, the mixture was concentrated under reduced pressure, the residue taken up in EtOAc (10 mL) and subsequently washed with saturated aqueous NH4Cl (10 mL), saturated aqueous NaHCO3 (3 * 15 mL) and brine (3 * 10 mL). After drying over Na2SO4, the mixture was concentrated to dryness to give the pure methyl ester. Experimental data are in accordance with literature. 19 Yield 60percent; mp 73-75 °C.
With dmap; dicyclohexyl-carbodiimide; In dichloromethane; at 20℃; for 2.5h;Inert atmosphere; To a suspension of 5-methoxy-3-indolylacetic acid (500 mg, 2.44 mmol) in CH2CI2 (7 mL) were added DCC (553 mg, 2.68 mmol), DMAP (30 mg, 0.244 mmol) and methanol (99 mu, 2.44 mmol). The resulting white suspension was stirred at RT under nitrogen for 2.5 h. The mixture was filtered and the filtrate concentrated to give a brown oil which was purified by flash column chromatography on silica gel (c-hexane to c-hexane/ EtOAc 8-2) to afford the desired material as a brown oil. TLC, Rf (EtOAc) = 0.82; MS (LC-MS): 220.0 [M+H]+, 242.1 [M+Na]+, 461.0 [2M+Na]+, 218.1 [M-H]-; tR (HPLC conditions f) 3.2 min.

  • 2
  • [ 23304-48-5 ]
  • [ 3471-31-6 ]
YieldReaction ConditionsOperation in experiment
27.2% With water; lithium hydroxide; In methanol; at 20℃; for 3h; 5-Methoxy-3-indoleacetic acid (compound No.36) Synthesis of Compound No.5 5-Methoxy-3-indoleacetic acid methyl ester (60.0 mg, 0.27 mmol) was dissolved in methanol (2 ml). To the solution, lithium hydroxide (19.7 mg, 0.82 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was acidified (pH=3 to 4) by the addition of 6 N hydrochloric acid, and the solvent was distilled off under reduced pressure. Water (5 ml) was added to the residue, followed by extraction with ethyl acetate (5 ml) three times. The organic layer was washed twice with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified by silica gel column chromatography (chloroform:methanol=9:1) to obtain 5-methoxy-3-indoleacetic acid (compound No.36) (15.3 mg, yield: 27.2%); Melting point: 147.0 to 149.8 C.; 1H NMR (400 MHz, CDCl3): delta 7.28 (d, J=8.8 Hz, 1H), 7.26 (s, 1H), 7.11 (d, J=2.3 Hz, 1H), 6.77 (dd, J=8.8, 2.3 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 1H); 13C NMR (100 MHz, CDCl3): delta 173.3, 154.8, 132.6, 128.9, 125.2, 112.7, 112.4, 108.8, 101.4, 55.8, 31.5; IR (neat): 3359, 2996, 2851, 1705, 1456, 1137 cm-1; EI-MS m/z [M]+ 205 (75%), 160; HREI-MS: m/z [M]+ calcd for 205.0739 (C11H11NO3), found, 205.0737.
27.2% With water; lithium hydroxide; In methanol; at 20℃; for 3h;Inert atmosphere; 5-Methoxy-3-indoleacetic acid (Compound No.36) 5-Methoxy-3-indoleacetic acid methyl ester (60.0 mg, 0.27 mmol) was dissolved in methanol (2 ml). To the solution, lithium hydroxide (19.7 mg, 0.82 mmol) was added, and the mixture was stirred at room temperature for 3 hours. After the reaction was confirmed by TLC to be complete, the reaction solution was rendered acidic (pH=3 to 4) by the addition of 6 N hydrochloric acid, and the solvent was distilled off under reduced pressure. Water (5 ml) was added to the residue, followed by extraction with ethyl acetate (5 ml) three times. The organic layer was washed twice with saturated saline and dehydrated over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then, the residue was purified using silica gel column chromatography (chloroform:methanol=9:1) to obtain 5-methoxy-3-indoleacetic acid (compound No.36) (15.3 mg, yield: 27.2%); Melting point: 147.0 to 149.8 C.; 1H NMR (400 MHz, CDCl3): delta 7.28 (d, J=8.8 Hz, 1H), 7.26 (s, 1H), 7.11 (d, J=2.3 Hz, 1H), 6.77 (dd, J=8.8, 2.3 Hz, 1H), 3.80 (s, 3H), 3.71 (s, 1H); 13C NMR (100 MHz, CDCl3): delta 173.3, 154.8, 132.6, 128.9, 125.2, 112.7, 112.4, 108.8, 101.4, 55.8, 31.5; IR (neat): 3359, 2996, 2851, 1705, 1456, 1137 cm-1; EI-MS m/z [M]+205 (75%), 160; HREI-MS found m/z 205.0737 [M]+, calcd for 205.0739 (C11H11NO3).
  • 3
  • [ 3471-31-6 ]
  • [ 74-88-4 ]
  • [ 23304-48-5 ]
YieldReaction ConditionsOperation in experiment
94% With potassium carbonate; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; Synthesis of 2-(5-methoxy-1-methyl-1H-indol-3-yl)acetic acid (Example 13)Step 1: To a stirred suspension of <strong>[3471-31-6]2-<strong>[3471-31-6](5-methoxy-1H-indol-3-yl)acetic acid</strong></strong> (2 g, 9.75 mmol), K2CO3 (4.03 g, 29.24 mmol) in dimethylformamide (20 mL) at 0° C., methyl iodide (1.51 mL, 24.39 mmol) was added slowly and the mixture was stirred at room temperature for 2 h until complete consumption of starting material. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (2.x.30 mL). The ethyl acetate layer was washed with water (2.x.10 mL), brine (10 mL), dried over anhydrous Na2SO4, filtered and concentrated. The obtained crude compound was purified by column chromatography (100-200 mesh silica gel) using 12percent EtOAc in petroleum ether as eluent to afford methyl 2-(5-methoxy-1H-indol-3-yl)acetate (2.0 g, 94percent) pale brown liquid. (TLC solvent system: 50percent EtOAc-petroleum ether; Rf: 0.5; UV 254 nm), (VRR-A1740-102).
94% With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 2h; To a stirred suspension of 2-(5-methoxy-1 H-indol-3-yl)acetic acid (2 g, 9.75 mmol), K2C03 (4.03 g, 29.24 mmol) in dimethylformamide (20 mL) at 0°C, methyl iodide (1.51 mL, 24.39 mmol) was added slowly and the mixture was stirred at room temperature for 2 h until complete consumption of starting material. The reaction mixture was diluted with water (20 mL), extracted with ethyl acetate (2x30 mL). The ethyl acetate layer was washed with water (2x10 mL), brine (10 mL), dried over anhydrous Na2S04, filtered and concentrated. The obtained crude compound was purified by column chromatography (100-200 mesh silica gel) using 12percent EtOAc in petroleum ether as eluent to afford methyl 2-(5-methoxy-1 H-indol-3- yl)acetate (2.0 g, 94percent) pale brown liquid. (TLC solvent system: 50percent EtOAc-petroleum ether; R,: 0.5; UV 254 nm), (VRR-A1740-102).
 

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