2-bromoethoxy-tert-butyl-diphenylsilane

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:0.00; pressure:0.00; stir:

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2.00 g (4.66 mmol) of 2-(4-hydroxyphenyl)-3-[4-[2-(1-pyrrolidinyl)ethoxy]benzyl]benzo[b]thiophene, 1.86 g (5.12 mmol) of 1-bromo-2-(tert-butyldiphenyl-silyloxy)ethane, and 1.93 g (14.0 mmol) of K2CO3 in 50 mL DMF was heated to 50° C. for 22 h. The reaction was poured into 250 mL of H2O and the mixture extracted with EtOAc (3×100 mL). The combined organic extracts were washed with H2O (2×100 mL), dried over K2CO3, filtered and concentrated in vacuo to give 4.21 g of an oily solid. Purification by flash chromatography (SiO2; 0.1% then 0.2% then 0.5% MeOH in CHCl3 sat'd with NH4OH) afforded 2.76 g (3.88 mmol; 83%) of the title compound as an oil. the mixture extracted with EtOAc (3×100 mL) The combined organic extracts were washed with H2O (2×100 mL) dried over K2CO3 filtered concentrated in vacuo

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

Procedure: A mixture of tert-butyldiphenylsilyl chloride (20.32 g, 74.03 mmol) and imidazole (6.25 g, 91.9 mmol) was treated dropwise with 2-bromoethanol (47, 5 mL, 8.87 g, 70.8 mmol). Stirring was continued for 12 h. The mixture was diluted with Et2O and water. The phases were separated, and the aqueous layer was extracted Et2O. The organic extract was washed with water and dried over Na2SO4. Concentration of the sample yielded a pale brown oil (26.01 g, 97%): 1H NMR δ 1.11 (s, 9H), 3.45 (t, J=6.3 Hz, 2H), 3.96 (t, J=6.3 Hz, 2H), 7.42-7.47 (m, 6H), 7.70-7.73 (m, 4H); 13C NMR δ 19.52, 27.03, 33.43, 64.24, 128.04, 130.10, 133.49, 135.84. The phases were separated the aqueous layer was extracted Et2O The organic extract was washed with water dried over Na2SO4

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 300 mg (corresponding to 0.893 mmol) of 2-(3′-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyridine was dissolved in 5.0 mL of dimethylformamide, and 370 mg (corresponding to 2.68 mmol) of potassium carbonate was added thereto. Then, 357 mg (corresponding to 0.982 mmol) of 1-bromo-2-(t-butyldiphenylsiloxy)ethane was added thereto. After the reaction mixture was stirred at 90° C. for 2 hours, a saturated sodium chloride aqueous solution was added, and extracted three times with ethyl acetate. The combined ethyl acetate layers were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1) to obtain 477 mg (corresponding to 0.771 mmol) of 2-[3′-(2″-t-butyldiphenylsiloxyethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine (FIG. 8, Step 4). extracted three times with ethyl acetate The combined ethyl acetate layers were dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Separately, 2.50 g (corresponding to 20.0 mmol) of 2-bromoethanol and 2.72 g (corresponding to 40.0 mmol) of imidazole were dissolved in 10 mL of dimethylformamide, and cooled to 0° C. Then, 5.50 g (corresponding to 20.0 mmol) of t-butyldiphenylchlorosilane was added thereto. After the reaction mixture was stirred at room temperature for 18 hours, a saturated sodium chloride aqueous solution was added, and extracted three times with ethyl acetate. The combined ethyl acetate layers were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1) to obtain 7.04 g (corresponding to 19.4 mmol) of 1-bromo-2-(t-butyldiphenylsiloxy)ethane (FIG. 8, Step 3). extracted three times with ethyl acetate The combined ethyl acetate layers were dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 mg (corresponding to 0.595 mmol) of 2-(4′-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyridine was dissolved in 3.0 mL of dimethylformamide, and 247 mg (corresponding to 1.79 mmol) of potassium carbonate was added thereto. Then, 259 mg (corresponding to 0.714 mmol) of 1-bromo-2-(t-butyldiphenylsiloxy)ethane was added thereto. After the reaction mixture was stirred at 90° C. for 2 hours, a saturated sodium chloride aqueous solution was added, and extracted three times with ethyl acetate. The combined ethyl acetate layers were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1) to obtain 368 mg (corresponding to 0.595 mmol) of 2-[4′-(2″-t-butyldiphenylsiloxyethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine (FIG. 1, Step 4). extracted three times with ethyl acetate The combined ethyl acetate layers were dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=2/1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Separately, 2.50 g (corresponding to 20.0 mmol) of 2-bromoethanol and 2.72 g (corresponding to 40.0 mmol) of imidazole were dissolved in 10 mL of dimethylformamide (DMF), and cooled to 0° C. Then, 5.50 g (corresponding to 20.0 mmol) of t-butyldiphenylchlorosilane (TBDPSCl) was added thereto. After the reaction mixture was stirred at room temperature for 18 hours, a saturated sodium chloride aqueous solution was added, and extracted three times with ethyl acetate. The combined ethyl acetate layers were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1) to obtain 7.04 g (corresponding to 19.4 mmol) of 1-bromo-2-(t-butyldiphenylsiloxy)ethane (FIG. 1, Step 3). extracted three times with ethyl acetate The combined ethyl acetate layers were dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=10/1)

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

Procedure: A mixture of tert-butyldiphenylsilyl chloride (20.32 g, 74.03 mmol) and imidazole (6.25 g, 91.9 mmol) was treated dropwise with 2-bromoethanol (47, 5 mL, 8.87 g, 70.8 mmol). Stirring was continued for 12 h. The mixture was diluted with Et2O and water. The phases were separated, and the aqueous layer was extracted Et2O. The organic extract was washed with water and dried over Na2SO4. Concentration of the sample yielded a pale brown oil (26.01 g, 97%): 1H NMR δ 1.11 (s, 9H), 3.45 (t, J=6.3 Hz, 2H), 3.96 (t, J=6.3 Hz, 2H), 7.42-7.47 (m, 6H), 7.70-7.73 (m, 4H); 13C NMR δ 19.52, 27.03, 33.43, 64.24, 128.04, 130.10, 133.49, 135.84. The phases were separated the aqueous layer was extracted Et2O The organic extract was washed with water dried over Na2SO4

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 300 mg (corresponding to 0.893 mmol) of 2-(3′-hydroxyphenyl)-6-iodoimidazo[1,2-a]pyridine was dissolved in 5.0 mL of dimethylformamide, and 370 mg (corresponding to 2.68 mmol) of potassium carbonate was added thereto. Then, 357 mg (corresponding to 0.982 mmol) of 1-bromo-2-(t-butyldiphenylsiloxy)ethane was added thereto. After the reaction mixture was stirred at 90° C. for 2 hours, a saturated sodium chloride aqueous solution was added, and extracted three times with ethyl acetate. The combined ethyl acetate layers were dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1) to obtain 477 mg (corresponding to 0.771 mmol) of 2-[3′-(2″-t-butyldiphenylsiloxyethoxy)phenyl]-6-iodoimidazo[1,2-a]pyridine (FIG. 8, Step 4). extracted three times with ethyl acetate The combined ethyl acetate layers were dried over anhydrous sodium sulfate concentrated under reduced pressure The resulting crude product was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=3/1)