1-(1-bromoethyl)-4-chlorobenzene

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-methyl-1H-indole-3-carboxylate (250 mg, 1.23 mmol) in anhydrous DMF (2 mL) was added NaH (60% in mineral oil, 74 mg, 1.85 mmol) at room temperature under N2. The reaction was stirred at 50-60° C. for 30 min. Then the reaction was cooled to 0° C. and a solution of 1-(1-bromoethyl)-4-chlorobenzene (from Example 35; 400 mg, 1.85 mmol) in DMF (1 mL) was added drop-wise. The reaction was stirred at room temperature overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic extract was combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography using an eluent of petroleum ether/EtOAc (60:1) to afford the title compound as a yellow oil. (210 mg, yield 50.1%) 1H NMR (Methanol-d4, 400 MHz) δ 8.07-8.04 (m, 1H), 7.33-7.29 (m, 2H), 7.16-7.15 (m, 2H), 7.14-7.08 (m, 1H) 7.07-6.96 (m, 2H), 5.97 (q, J=7.2 Hz, J2=14.4 Hz, 1H), 4.37 (d, J=7.2 Hz, 2H), 2.76 (m, 3H), 1.95 (d, J=6.8 Hz, 3H), 1.43 (d, J=14.0 Hz, 3H). Then the reaction was cooled to 0° C. The reaction was stirred at room temperature overnight extracted with EtOAc The organic extract dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel chromatography

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-methyl-1H-indole-3-carboxylate (250 mg, 1.23 mmol) in anhydrous DMF (2 mL) was added NaH (60% in mineral oil, 74 mg, 1.85 mmol) at room temperature under N2. The reaction was stirred at 50-60° C. for 30 min. Then the reaction was cooled to 0° C. and a solution of 1-(1-bromoethyl)-4-chlorobenzene (from Example 35; 400 mg, 1.85 mmol) in DMF (1 mL) was added drop-wise. The reaction was stirred at room temperature overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic extract was combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography using an eluent of petroleum ether/EtOAc (60:1) to afford the title compound as a yellow oil. (210 mg, yield 50.1%) 1H NMR (Methanol-d4, 400 MHz) δ 8.07-8.04 (m, 1H), 7.33-7.29 (m, 2H), 7.16-7.15 (m, 2H), 7.14-7.08 (m, 1H) 7.07-6.96 (m, 2H), 5.97 (q, J=7.2 Hz, J2=14.4 Hz, 1H), 4.37 (d, J=7.2 Hz, 2H), 2.76 (m, 3H), 1.95 (d, J=6.8 Hz, 3H), 1.43 (d, J=14.0 Hz, 3H). Then the reaction was cooled to 0° C. The reaction was stirred at room temperature overnight extracted with EtOAc The organic extract dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel chromatography

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-methyl-1H-indole-3-carboxylate (250 mg, 1.23 mmol) in anhydrous DMF (2 mL) was added NaH (60% in mineral oil, 74 mg, 1.85 mmol) at room temperature under N2. The reaction was stirred at 50-60° C. for 30 min. Then the reaction was cooled to 0° C. and a solution of 1-(1-bromoethyl)-4-chlorobenzene (from Example 35; 400 mg, 1.85 mmol) in DMF (1 mL) was added drop-wise. The reaction was stirred at room temperature overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic extract was combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography using an eluent of petroleum ether/EtOAc (60:1) to afford the title compound as a yellow oil. (210 mg, yield 50.1%) 1H NMR (Methanol-d4, 400 MHz) δ 8.07-8.04 (m, 1H), 7.33-7.29 (m, 2H), 7.16-7.15 (m, 2H), 7.14-7.08 (m, 1H) 7.07-6.96 (m, 2H), 5.97 (q, J=7.2 Hz, J2=14.4 Hz, 1H), 4.37 (d, J=7.2 Hz, 2H), 2.76 (m, 3H), 1.95 (d, J=6.8 Hz, 3H), 1.43 (d, J=14.0 Hz, 3H). Then the reaction was cooled to 0° C. The reaction was stirred at room temperature overnight extracted with EtOAc The organic extract dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel chromatography

Conditions: temp:55.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of ethyl 2-methyl-1H-indole-3-carboxylate (250 mg, 1.23 mmol) in anhydrous DMF (2 mL) was added NaH (60% in mineral oil, 74 mg, 1.85 mmol) at room temperature under N2. The reaction was stirred at 50-60° C. for 30 min. Then the reaction was cooled to 0° C. and a solution of 1-(1-bromoethyl)-4-chlorobenzene (from Example 35; 400 mg, 1.85 mmol) in DMF (1 mL) was added drop-wise. The reaction was stirred at room temperature overnight. Then the mixture was diluted with water and extracted with EtOAc. The organic extract was combined, dried over Na2SO4 and concentrated in vacuo. The residue was purified by silica gel chromatography using an eluent of petroleum ether/EtOAc (60:1) to afford the title compound as a yellow oil. (210 mg, yield 50.1%) 1H NMR (Methanol-d4, 400 MHz) δ 8.07-8.04 (m, 1H), 7.33-7.29 (m, 2H), 7.16-7.15 (m, 2H), 7.14-7.08 (m, 1H), 7.07-6.96 (m, 2H), 5.97 (q, J=7.2 Hz, J2=14.4 Hz, 1H), 4.37 (d, J=7.2 Hz, 2H), 2.76 (m, 3H), 1.95 (d, J=6.8 Hz, 3H), 1.43 (d, J=14.0 Hz, 3H). Then the reaction was cooled to 0° C. The reaction was stirred at room temperature overnight extracted with EtOAc The organic extract dried over Na2SO4 concentrated in vacuo The residue was purified by silica gel chromatography

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

Procedure: To a solution of the above product 1-(4-chlorophenyl)ethanol in 100 ml of diethyl ether was slowly added a solution of 13.5 g (50 mmoles) of phosphorus tribromide in 50 ml of diethyl ether. The resulting solution was stirred overnight at room temperature. The reaction mixture was poured into ice water. Sodium hydrogencarbonate was added to the resulting solution for neutralization, and the organic layer was extracted with diethyl ether. The organic layer was collected, washed with water, dried over anhydrous sodium sulfate and concentrated in a vacuum, giving 9.00 g (41 mmoles, 82% in yield) of 1-(1-bromoethyl)-4-chlorobenzene [1H-NMR (300 MHz, CDCl3) 2.02 (d, J=6.9 Hz, 3H), 5.1 (q, J=6.9 Hz, 1H), 7.26-7.40 (m, 4H)] in a nearly pure form. the organic layer was extracted with diethyl ether The organic layer was collected washed with water dried over anhydrous sodium sulfate concentrated in a vacuum

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

Procedure: To a solution of the above product 1-(4-chlorophenyl)ethanol in 100 ml of diethyl ether was slowly added a solution of 13.5 g (50 mmoles) of phosphorus tribromide in 50 ml of diethyl ether. The resulting solution was stirred overnight at room temperature. The reaction mixture was poured into ice water. Sodium hydrogencarbonate was added to the resulting solution for neutralization, and the organic layer was extracted with diethyl ether. The organic layer was collected, washed with water, dried over anhydrous sodium sulfate and concentrated in a vacuum, giving 9.00 g (41 mmoles, 82% in yield) of 1-(1-bromoethyl)-4-chlorobenzene [1H-NMR (300 MHz, CDCl3) 2.02 (d, J=6.9 Hz, 3H), 5.1 (q, J=6.9 Hz, 1H), 7.26-7.40 (m, 4H)] in a nearly pure form. the organic layer was extracted with diethyl ether The organic layer was collected washed with water dried over anhydrous sodium sulfate concentrated in a vacuum