4-bromo-2-cyclopentyloxy-1-methoxybenzene

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:0.00; pressure:0.00; stir:

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

Procedure: A solution of 5-bromo-2-methoxyphenol (1 g), cyclopentanol (0.54 ml) and triphenylphosphine (1.55 g) in anhydrous tetrahydrofuran (20 ml), at 0° C., was treated with diethylazodicarboxylate (0.85 mi). The resulting yellow solution was stirred at 0° C. for 40 minutes then evaporated. The residue was subjected to flash chromatography on silica eluting with a mixture of petroleum ether and ethyl acetate (19:1, v/v) to give the title compound (1.2 g) as a pale yellow oil. NMR (CDCl3): δ1.62 (m,2H), 1.78-2.20 (m,6H), 3.79 (s,3H), 4.72 (m,1H), 6.70 (d,1H), 7.00 (dd,2H). Mass spectrum (FAB): m/z 270/272 (M)+. then evaporated The residue was subjected to flash chromatography on silica eluting with a mixture of petroleum ether and ethyl acetate (19:1

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of butyl lithium in hexane (5.1 mL; 2.5 M) is treated with a solution of 3-cyclopentyloxy-4-methoxyphenyl bromide (3.45 g) in dry tetrahydrofuran (30 mL) at -70° C. and the solution is then stirred at -70° C. for 1 hour. It is then treated dropwise with 2,6-dichlorophenylacetaldehyde (2.4 g), while keeping the temperature below -60° C. When the addition is complete the temperature is allowed to rise to room temperature and the solution is stirred for a further 2 hours. The reaction mixture is treated with aqueous ammonium chloride solution (50 mL) and the solution is extracted with diethyl ether (2×200 mL). The combined extracts are dried and concentrated, to give a yellow oil, which is subjected to flash chromatography, eluting with a mixture of diethyl ether and pentane (1:8 v/v), to give 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(2,6-dichlorophenyl)ethanol (1.6 g),in the form of a white solid, m.p. 87°-89° C. the temperature below -60° C When the addition to rise to room temperature the solution is stirred for a further 2 hours the solution is extracted with diethyl ether (2×200 mL) The combined extracts are dried concentrated to give a yellow oil, which eluting with a mixture of diethyl ether and pentane (1:8 v/v)

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

Procedure: A stirred solution of 5-bromo-2-methoxyphenol (74 g) and anhydrous potassium carbonate (73.6 g) in dry dimethylformamide (500 mL) is treated with cyclopentyl bromide (80.5 g) and the solution is heated at 60° C. for 16 hours. It is then concentrated, and the resulting residue is triturated with water (250 mL), and extracted with dichloromethane (3×250 mL). The combined extracts are dried and evaporated, to give 3-cyclopentyloxy-4-methoxyphenyl bromide (95.5 g), in the form of a light brown oil. It is then concentrated the resulting residue is triturated with water (250 mL) extracted with dichloromethane (3×250 mL) The combined extracts are dried evaporated

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

Procedure: Following the procedure of Example 1, phenylboronic acid and 3-cyclopentyloxy-4-methoxybromobenzene yielded 46% of the title compound as white needles: mp 62°-64° C.

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

Procedure: Following the procedure of Example 1, phenylboronic acid and 3-cyclopentyloxy-4-methoxybromobenzene yielded 46% of the title compound as white needles: mp 62°-64° C.

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

Procedure: Following the procedure of Example 1, 4-chloro-phenylboronic acid and 3-cyclopentyloxy-4-methoxybromobenzene yielded 92% of the title compound as white needles: mp 94°-95° C.

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

Procedure: Following the procedure of Example 1, 4-chloro-phenylboronic acid and 3-cyclopentyloxy-4-methoxybromobenzene yielded 92% of the title compound as white needles: mp 94°-95° C.