No renderable structure data available
COC(=O)C1=CC2=C(N1)C=C(C=C2Br)FChemical Intermediate
Structures, identifiers and computed properties have been matched to the database record by CAS.
| Intermediates | methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate |
|---|---|
| IUPAC Name | — |
| CAS Number | 476618-03-8 |
| Database ID | 21867463 |
| Molecular Formula | — |
| Molecular Weight | — |
Product Information
methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (CAS 476618-03-8) product identity, structure identifiers and related reaction data for chemical intermediate research and sourcing review.
Potential Applications
For professional research and industrial use only
Database ID 21867463
Safety Notice
For professional research and industrial use only. Review the supplier safety data sheet before handling.
Synthesis data
12 reactions · 12 references
Conditions: temp:0.00; pressure:0.00; stir:
Source ID: ord-2dd920059367484dbd7adaebb91f5cedConditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (10 g, 36.8 mmol) in DMF (100 mL) at 0° C. was added NaH (1.8 g, 44.2 mmol, 60% in oil). The mixture was stirred at r.t. for 30 minutes and tetra-n-butylammonium iodide (500 mg) was added, followed by the addition of ethyl 4-bromobutyrate (10.1 g, 51.5 mmol). The reaction mixture was stirred at r.t. for 3 h, poured into saturated aqueous NH4Cl and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 20% EtOAc to give 13.2 g of the title compound. The reaction mixture was stirred at r.t. for 3 h the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried over Na2SO4 concentrated The residue was purified by silica gel chromatography eluted with 20% EtOAc
Source ID: ord-1cb1a896013746d3859385f2d7568f03Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (10 g, 36.8 mmol) in DMF (100 mL) at 0° C. was added NaH (1.8 g, 44.2 mmol, 60% in oil). The mixture was stirred at r.t. for 30 minutes and tetra-n-butylammonium iodide (500 mg) was added, followed by the addition of ethyl 4-bromobutyrate (10.1 g, 51.5 mmol). The reaction mixture was stirred at r.t. for 3 h, poured into saturated aqueous NH4Cl and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 20% EtOAc to give 13.2 g of the title compound. The reaction mixture was stirred at r.t. for 3 h the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried over Na2SO4 concentrated The residue was purified by silica gel chromatography eluted with 20% EtOAc
Source ID: ord-1cb1a896013746d3859385f2d7568f03Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (3 g, 11 mmol) in THF (50 mL) at −30° C. was added diisobutylaluminum hydride (33 mmol, 1.5M toluene solution). The mixture was stirred for 1 hour at −30° C. and 1N HCl was added. The phases were separated and the aqueous layer was extracted with Et2O. The combined organic layers were dried over Na2SO4 and concentrated to give 2.6 g of the title compound used as such. The phases were separated the aqueous layer was extracted with Et2O The combined organic layers were dried over Na2SO4 concentrated
Source ID: ord-62c19ebd538d4c77bd4a41527a3c3744Conditions: temp:-30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (3 g, 11 mmol) in THF (50 mL) at −30° C. was added diisobutylaluminum hydride (33 mmol, 1.5M toluene solution). The mixture was stirred for 1 hour at −30° C. and 1N HCl was added. The phases were separated and the aqueous layer was extracted with Et2O. The combined organic layers were dried over Na2SO4 and concentrated to give 2.6 g of the title compound used as such. The phases were separated the aqueous layer was extracted with Et2O The combined organic layers were dried over Na2SO4 concentrated
Source ID: ord-62c19ebd538d4c77bd4a41527a3c3744Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a suspension of the indole of Step 4 (4 g, 15 mmol) in a mixture of 10:1 toluene/THF (100 mL) at r.t. was added potassium t-butoxide (15 mL of a 1M solution in THF). The reaction mixture was stirred for 2 minutes and methyl acrylate (2.5 g, 30 mmol) was added. The mixture was stirred at reflux for 5 hours and cooled to r.t. Then 1N HCl was added to acidify to pH 3 and the reaction mixture was extracted with EtOAc and the combined organic layers were concentrated. The residue was swished in EtOAc/Hexanes to give 4 g of the desired compound as a pale yellow solid. The mixture was stirred at reflux for 5 hours the reaction mixture was extracted with EtOAc the combined organic layers were concentrated
Source ID: ord-c9e472e8bbb3439bab0a1350f149cf54Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a suspension of the indole of Step 4 (4 g, 15 mmol) in a mixture of 10:1 toluene/THF (100 mL) at r.t. was added potassium t-butoxide (15 mL of a 1M solution in THF). The reaction mixture was stirred for 2 minutes and methyl acrylate (2.5 g, 30 mmol) was added. The mixture was stirred at reflux for 5 hours and cooled to r.t. Then 1N HCl was added to acidify to pH 3 and the reaction mixture was extracted with EtOAc and the combined organic layers were concentrated. The residue was swished in EtOAc/Hexanes to give 4 g of the desired compound as a pale yellow solid. The mixture was stirred at reflux for 5 hours the reaction mixture was extracted with EtOAc the combined organic layers were concentrated
Source ID: ord-c9e472e8bbb3439bab0a1350f149cf54Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of 4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester (178 mg, 0.65 mmol) in 5 ml anhydrous dimethylformanide was added sodium hydride (52 mg of a 60% suspension in mineral oil, 1.3 mmol) portionwise at 0° C. The solution was stirred with a magnetic stirrer at 0° C. for 20 minutes. Benzyl bromide (0.17 ml, 1.43 mmol) was added in one portion and the reaction mixture was stirred at 0° C. for 30 minutes. The solution was allowed to warm to room temperature and the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by Preparative TLC (10% Ethyl acetate/Hexane) to give 80 mg 1-Benzyl-4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester as a yellow solid (34%). 1H NMR (CDCl3, 300 MHz) δ: 3.89 (s, 3H), 5.78 (s, 2H), 7.17 (m, 8H). the reaction mixture was stirred at 0° C. for 30 minutes to warm to room temperature the reaction mixture was partitioned between water and ethyl acetate The aqueous layer was extracted with ethyl acetate the combined organic fractions were washed with water and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by Preparative TLC (10% Ethyl acetate/Hexane)
Source ID: ord-2e46238c6c614721b0f002b39e2ceb4aConditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: Dry methanol (5 ml) and NaOMe (0.9 ml, 3.93 mmol, 25% wt in MeOH) were added to a three-neck flask equipped with stirrer, low-temperature thermometer, and nitrogen line. The resulting solution was cooled in a dry ice/CH3CN bath to −40° C. A solution of 2-bromo-4-fluoro-benzaldehyde (195 mg, 0.96 mmol) and methyl azidoacetate (450 mg, 3.9 mmol) in dry MeOH (5 ml) was added dropwise. The mixture was allowed to stir at −40° C. for 30 minutes before warming up to room temperature. After stirring another 3 hours, the reaction solvent was removed under reduced pressure. The residue was added to xylene (15 ml), and the organic phase was washed with H2O, brine, followed by drying over MgSO4. The resulting solution was added dropwise to a flask of xylene (30 ml) and the solution was heated at reflux overnight. After cooling to room temperature, the reaction mixture was washed with H2O, and xylene was removed under reduced pressure to give 4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester as a white solid (178 mg, 68%). MS: 272.1 (M−H)−. equipped with stirrer before warming up to room temperature After stirring another 3 hours the reaction solvent was removed under reduced pressure The residue was added to xylene (15 ml) the organic phase was washed with H2O, brine by drying over MgSO4 The resulting solution was added dropwise to a flask of xylene (30 ml) the solution was heated at reflux overnight After cooling to room temperature the reaction mixture was washed with H2O, and xylene was removed under reduced pressure
Source ID: ord-3f5216aaf48543b98c181b7f02cfd30dConditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of 4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester (178 mg, 0.65 mmol) in 5 ml anhydrous dimethylformanide was added sodium hydride (52 mg of a 60% suspension in mineral oil, 1.3 mmol) portionwise at 0° C. The solution was stirred with a magnetic stirrer at 0° C. for 20 minutes. Benzyl bromide (0.17 ml, 1.43 mmol) was added in one portion and the reaction mixture was stirred at 0° C. for 30 minutes. The solution was allowed to warm to room temperature and the reaction mixture was partitioned between water and ethyl acetate. The aqueous layer was extracted with ethyl acetate and the combined organic fractions were washed with water and brine. After drying over MgSO4, the organic fraction was concentrated in vacuo and resulting brown residue was purified by Preparative TLC (10% Ethyl acetate/Hexane) to give 80 mg 1-Benzyl-4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester as a yellow solid (34%). 1H NMR (CDCl3, 300 MHz) δ: 3.89 (s, 3H), 5.78 (s, 2H), 7.17 (m, 8H). the reaction mixture was stirred at 0° C. for 30 minutes to warm to room temperature the reaction mixture was partitioned between water and ethyl acetate The aqueous layer was extracted with ethyl acetate the combined organic fractions were washed with water and brine After drying over MgSO4 the organic fraction was concentrated in vacuo resulting brown residue was purified by Preparative TLC (10% Ethyl acetate/Hexane)
Source ID: ord-2e46238c6c614721b0f002b39e2ceb4aConditions: temp:-40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: Dry methanol (5 ml) and NaOMe (0.9 ml, 3.93 mmol, 25% wt in MeOH) were added to a three-neck flask equipped with stirrer, low-temperature thermometer, and nitrogen line. The resulting solution was cooled in a dry ice/CH3CN bath to −40° C. A solution of 2-bromo-4-fluoro-benzaldehyde (195 mg, 0.96 mmol) and methyl azidoacetate (450 mg, 3.9 mmol) in dry MeOH (5 ml) was added dropwise. The mixture was allowed to stir at −40° C. for 30 minutes before warming up to room temperature. After stirring another 3 hours, the reaction solvent was removed under reduced pressure. The residue was added to xylene (15 ml), and the organic phase was washed with H2O, brine, followed by drying over MgSO4. The resulting solution was added dropwise to a flask of xylene (30 ml) and the solution was heated at reflux overnight. After cooling to room temperature, the reaction mixture was washed with H2O, and xylene was removed under reduced pressure to give 4-bromo-6-fluoro-1H-indole-2-carboxylic acid methyl ester as a white solid (178 mg, 68%). MS: 272.1 (M−H)−. equipped with stirrer before warming up to room temperature After stirring another 3 hours the reaction solvent was removed under reduced pressure The residue was added to xylene (15 ml) the organic phase was washed with H2O, brine by drying over MgSO4 The resulting solution was added dropwise to a flask of xylene (30 ml) the solution was heated at reflux overnight After cooling to room temperature the reaction mixture was washed with H2O, and xylene was removed under reduced pressure
Source ID: ord-3f5216aaf48543b98c181b7f02cfd30dConditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.
Procedure: To a solution of methyl 4-bromo-6-fluoro-1H-indole-2-carboxylate (10 g, 36.8 mmol) in DMF (100 mL) at 0° C. was added NaH (1.8 g, 44.2 mmol, 60% in oil). The mixture was stirred at r.t. for 30 minutes and tetra-n-butylammonium iodide (500 mg) was added, followed by the addition of ethyl 4-bromobutyrate (10.1 g, 51.5 mmol). The reaction mixture was stirred at r.t. for 3 h, poured into saturated aqueous NH4Cl and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography eluted with 20% EtOAc to give 13.2 g of the title compound. The reaction mixture was stirred at r.t. for 3 h the aqueous layer was extracted with EtOAc The combined organic layers were washed with brine dried over Na2SO4 concentrated The residue was purified by silica gel chromatography eluted with 20% EtOAc
Source ID: ord-1cb1a896013746d3859385f2d7568f03PubChem References
These sources are listed in the compound's public database record.
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