2-(4-iodophenoxy)ethanol

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

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

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

Procedure: A solution of 4-(2-hydroxyethoxy)phenyl iodide (0.059 g, 0.22 mmol), and 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.080 g, 0.22 nmol) in dry piperidine (1 mL) was treated with a mixture of tetrakis(triphenylphosphine)palladium (0.013 g, 0.011 mmol), cuprous iodide (0.0025 g, 0.013 mmol), and triphenylphosphine (crystal), as described above in Example 11. Purification of the crude product by chromatography (silica gel, 1 to 2% methanol in methylene chloride) followed by pumping in vacuo afforded the titled intermediate as a viscous oil. 1H-NMR (400 MHz, CDCl3) δ 7.39 (d, J=9.0 Hz, 2H), 7.24 (d, J=2.1 Hz, 1H), 7.13 (d-d, J=8.3 Hz, J=2.1 Hz, 1H), 6.85 (d, J=8.7, 2H), 6.84 (d, J=8.3 Hz, 1H), 4.81 (p, J=2.0 Hz, 1H), 4.09 (t, J=4.4 Hz, 2H), 4.00 (s, 4H), 3.97 (t, J=4.4 Hz, 2H), 3.84 (s, 3H), 2.3 to 1.5 (m, 21H with H2O). Purification of the crude product by chromatography (silica gel, 1 to 2% methanol in methylene chloride)

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

Procedure: A melt of ethylene carbonate (6.5 g, 74 mmol) in a small flask under Argon was treated with 4-iodophenol (0.400 g, 1.82 mmol) and powdered potassium carbonate (1.26 g, 9.1 mmol) and was stirred at 90° C. for 3 hr. The mixture was treated with cold dilute hydrochloric acid to decompose the excess potassium carbonate and excess aqueous sodium hydroxide solution was slowly added and the mixture was stirred over night. The suspension was extracted with methylene chloride, was washed with water and brine, was dried over sodium sulfate and was stripped to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride to afford (0.128 g, 27%) of the titled intermediate as a white solid, mp 76°-77.5° C. was slowly added the mixture was stirred over night The suspension was extracted with methylene chloride was washed with water and brine was dried over sodium sulfate to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride

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

Procedure: Sodium (0.53 g) was dissolved in ethanol (50 ml) under nitrogen and 4-iodophenol (5.0 g), and 2-chloroethanol (3.93 g), were added successively. The mixture was refluxed for 18 h, treated with saturated aqueous ammonium chloride (50 ml) and evaporated. The aqueous residue was extracted with ER (3×100 ml) and the dried extract was evaporated onto silica (Merck 9385; 50 ml) and purified by [C] eluted with cyclohexane-ER (7:3) followed by cyclohexane-ER (1:1) to give the title compound (3.0 g) m.p. 76°-77°. The mixture was refluxed for 18 h evaporated The aqueous residue was extracted with ER (3×100 ml) the dried extract was evaporated onto silica (Merck 9385; 50 ml) purified by [C] eluted with cyclohexane-ER (7:3)

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

Procedure: The product was prepared analogously to Example 7.1e starting from 3-chloro-5-(4-chlorophenyl)-2-ethynylpyridine and 2-(4-iodophenoxy)ethanol. Yield: 0.48 g (66% of theoretical); C21H15Cl2NO2 (M=384.255); calc.: molpeak (M+H)+384/386/388 (2Cl); found: molpeak (M+H)+: 384/386/388 (2Cl); HPLC-MS: 6.24 minutes (method B). The product was prepared analogously to Example 7.1e 6.24 minutes (method B)

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

Procedure: The product was prepared analogously to Example 7.1e starting from 3-bromo-5-(4-chlorophenyl)-2-ethynylpyridine and 2-(4-iodophenoxy)ethanol. Yield: 0.18 g (28% of theoretical); C21H15BrClNO2 (M=428.706); calc.: molpeak (M+H)+: 428/430/432 (BrCl); found: molpeak (M+H)+: 428/430/432 (BrCl). The product was prepared analogously to Example 7.1e

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

Procedure: The product was prepared analogously to Example 7.1e starting from 3-bromo-5-(4-chlorophenyl)-2-ethynylpyridine and 2-(4-iodophenoxy)ethanol. Yield: 0.18 g (28% of theoretical); C21H15BrClNO2 (M=428.706); calc.: molpeak (M+H)+: 428/430/432 (BrCl); found: molpeak (M+H)+: 428/430/432 (BrCl). The product was prepared analogously to Example 7.1e

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

Procedure: A solution of 4-(2-hydroxyethoxy)phenyl iodide (0.059 g, 0.22 mmol), and 4-(3-cyclopentyloxy-4-methoxyphenyl)-1,1-(ethylenedioxy)-4-ethynylcyclohexane (0.080 g, 0.22 nmol) in dry piperidine (1 mL) was treated with a mixture of tetrakis(triphenylphosphine)palladium (0.013 g, 0.011 mmol), cuprous iodide (0.0025 g, 0.013 mmol), and triphenylphosphine (crystal), as described above in Example 11. Purification of the crude product by chromatography (silica gel, 1 to 2% methanol in methylene chloride) followed by pumping in vacuo afforded the titled intermediate as a viscous oil. 1H-NMR (400 MHz, CDCl3) δ 7.39 (d, J=9.0 Hz, 2H), 7.24 (d, J=2.1 Hz, 1H), 7.13 (d-d, J=8.3 Hz, J=2.1 Hz, 1H), 6.85 (d, J=8.7, 2H), 6.84 (d, J=8.3 Hz, 1H), 4.81 (p, J=2.0 Hz, 1H), 4.09 (t, J=4.4 Hz, 2H), 4.00 (s, 4H), 3.97 (t, J=4.4 Hz, 2H), 3.84 (s, 3H), 2.3 to 1.5 (m, 21H with H2O). Purification of the crude product by chromatography (silica gel, 1 to 2% methanol in methylene chloride)

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

Procedure: A melt of ethylene carbonate (6.5 g, 74 mmol) in a small flask under Argon was treated with 4-iodophenol (0.400 g, 1.82 mmol) and powdered potassium carbonate (1.26 g, 9.1 mmol) and was stirred at 90° C. for 3 hr. The mixture was treated with cold dilute hydrochloric acid to decompose the excess potassium carbonate and excess aqueous sodium hydroxide solution was slowly added and the mixture was stirred over night. The suspension was extracted with methylene chloride, was washed with water and brine, was dried over sodium sulfate and was stripped to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride to afford (0.128 g, 27%) of the titled intermediate as a white solid, mp 76°-77.5° C. was slowly added the mixture was stirred over night The suspension was extracted with methylene chloride was washed with water and brine was dried over sodium sulfate to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride

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

Procedure: A melt of ethylene carbonate (6.5 g, 74 mmol) in a small flask under Argon was treated with 4-iodophenol (0.400 g, 1.82 mmol) and powdered potassium carbonate (1.26 g, 9.1 mmol) and was stirred at 90° C. for 3 hr. The mixture was treated with cold dilute hydrochloric acid to decompose the excess potassium carbonate and excess aqueous sodium hydroxide solution was slowly added and the mixture was stirred over night. The suspension was extracted with methylene chloride, was washed with water and brine, was dried over sodium sulfate and was stripped to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride to afford (0.128 g, 27%) of the titled intermediate as a white solid, mp 76°-77.5° C. was slowly added the mixture was stirred over night The suspension was extracted with methylene chloride was washed with water and brine was dried over sodium sulfate to afford a white solid, which was purified by flash chromatography on silica gel (20 mL) with methylene chloride

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