4-bromo-6-methoxy-1H-indole

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Bromo-5-methoxy-phenyl)-N-hydroxy-acetamide (360 mg, 1.384 mmol) was dissolved in vinyl acetate (1.92 mL, 20.8 mmol), and Li2PdCl4 (18.2 mg, 69 μmol) was added. The reaction mixture was stirred for 3 hours at 60° C. The reaction mixture was diluted with EtOAc and brine; the organic layer was separated and concentrated under reduced pressure to give a solid, which was dissolved in 20 mL of MeOH. 1N aqueous NaOH (2.61 mL, 2.61 mmol) was added, and the reaction was stirred for two hours at room temperature. The reaction mixture was quenched by addition of 2 N aqueous HCl (1.3 mL, 2.6 mmol), followed by addition of 500 mg of Na2CO3. After addition of 50 mL of EtOAc, the organic layers were separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4) to yield the title compound as a liquid (145 mg, 46% over 2 steps). 1H-NMR (600 MHz; DMSO-d6): 11.26 (brs, 1H), 7.31 (dd, 1H), 6.93 (d, 1H), 6.90 (d, 1H), 6.29 (dd, 1H), 3.78 (s, 3H). the organic layer was separated concentrated under reduced pressure to give a solid, which the reaction was stirred for two hours at room temperature the organic layers were separated dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4)

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Bromo-5-methoxy-phenyl)-N-hydroxy-acetamide (360 mg, 1.384 mmol) was dissolved in vinyl acetate (1.92 mL, 20.8 mmol), and Li2PdCl4 (18.2 mg, 69 μmol) was added. The reaction mixture was stirred for 3 hours at 60° C. The reaction mixture was diluted with EtOAc and brine; the organic layer was separated and concentrated under reduced pressure to give a solid, which was dissolved in 20 mL of MeOH. 1N aqueous NaOH (2.61 mL, 2.61 mmol) was added, and the reaction was stirred for two hours at room temperature. The reaction mixture was quenched by addition of 2 N aqueous HCl (1.3 mL, 2.6 mmol), followed by addition of 500 mg of Na2CO3. After addition of 50 mL of EtOAc, the organic layers were separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4) to yield the title compound as a liquid (145 mg, 46% over 2 steps). 1H-NMR (600 MHz; DMSO-d6): 11.26 (brs, 1H), 7.31 (dd, 1H), 6.93 (d, 1H), 6.90 (d, 1H), 6.29 (dd, 1H), 3.78 (s, 3H). the organic layer was separated concentrated under reduced pressure to give a solid, which the reaction was stirred for two hours at room temperature the organic layers were separated dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-6-methoxy-indole CXIV (920 mg, 4.1 mmol), ethyl cinnamate (1.03 ml, 6.1 mmol), TEA (850 μl, 6.1 mmol), Pd(OAc)2 (46 mg, 0.20 mmol) and (o-Tol)3P (120 mg, 0.41 mmol) was heated in a sealed vial to 100° C. for 27 hours; The reaction mixture was cooled to room temperature, diluted with DCM, and the mixture was filtered through celite. The filtrate was concentrated and purified via flash chromatography (hexane/EtOAc) to afford 3-(6-methoxy-1H-Indol-4-yl)-3-phenyl-acrylic acid ethyl ester CXVI as a yellow-brown waxy solid (440 mg, 34% yield). The reaction mixture was cooled to room temperature the mixture was filtered through celite The filtrate was concentrated purified via flash chromatography (hexane/EtOAc)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-Bromo-6-methoxy indole (0.07 g, 0.3 mmol) was dissolved in dry dichloromethane (4 mL) and benzenesulphonyl chloride (0.06 g, 0.3 mmol), tetrabutylammonium hydrogen sulphate (0.01 g, 0.01 mmol) and 4N NaOH (0.5 mL) were added and the mixture was stirred at rt for 50 min. The mixture was extracted with water (2×4 mL), dried (Na2SO4) and evaporated. The crude product was combined with an earlier batch of this intermediate (followed this experimental and starting with 4-bromo-6-methoxy indole (0.35 g, 1.5 mmol). MS (ESI+) for C15H12BrNO3S m/z 366 (M+H)+. The mixture was extracted with water (2×4 mL) dried (Na2SO4) evaporated

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-(3-Bromo-5-methoxy-phenyl)-N-hydroxy-acetamide (360 mg, 1.384 mmol) was dissolved in vinyl acetate (1.92 mL, 20.8 mmol), and Li2PdCl4 (18.2 mg, 69 μmol) was added. The reaction mixture was stirred for 3 hours at 60° C. The reaction mixture was diluted with EtOAc and brine; the organic layer was separated and concentrated under reduced pressure to give a solid, which was dissolved in 20 mL of MeOH. 1N aqueous NaOH (2.61 mL, 2.61 mmol) was added, and the reaction was stirred for two hours at room temperature. The reaction mixture was quenched by addition of 2 N aqueous HCl (1.3 mL, 2.6 mmol), followed by addition of 500 mg of Na2CO3. After addition of 50 mL of EtOAc, the organic layers were separated, dried over Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4) to yield the title compound as a liquid (145 mg, 46% over 2 steps). 1H-NMR (600 MHz; DMSO-d6): 11.26 (brs, 1H), 7.31 (dd, 1H), 6.93 (d, 1H), 6.90 (d, 1H), 6.29 (dd, 1H), 3.78 (s, 3H). the organic layer was separated concentrated under reduced pressure to give a solid, which the reaction was stirred for two hours at room temperature the organic layers were separated dried over Na2SO4 filtered concentrated The residue was purified by column chromatography (20 g SiO2, EtOAc/heptane in a gradient from 0/100 to 1/4)