4-(chloromethyl)-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:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 3-cyclopentyloxy-4-methoxybenzyl chloride (119 grams, 0.49 mol), 120 milliliters of methylene chloride, KCN (70.7 grams, 1.09 mol), benzyltriethylammonium chloride (35 grams, 0.015 mol) and water (120 milliliters) was stirred vigorously at room temperature for 48 hours. The reaction mixture was diluted with methylene chloride and the layers were separated. The methylene chloride solution was extracted several times with water and evaporated to yield 3-cyclopentyloxy-4-methoxyphenylacetonitrile (109 grams, 95%) for the subsequent transformation. the layers were separated The methylene chloride solution was extracted several times with water evaporated

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

Procedure: A solution containing 3-cyclopentyloxy-4-methoxybenzyl alcohol (112 grams, 0.50 mol), prepared as described in step a), in 1 liter of methylene chloride was stirred at room temperature with concentrated HCl (110 milliliters, 1.2 mol) for 3 hours, at which time the reaction was done by TLC. The layers were separated and the methylene chloride solution was washed twice with water and evaporated under reduced pressure to give 3-cyclopentyloxy-4-methoxybenzyl chloride (119 grams, 100%). prepared The layers were separated the methylene chloride solution was washed twice with water evaporated under reduced pressure

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

Procedure: 6-ethylamino-8-isopropyl-3H-purine (7.52 g, 36.65 mmol) and 3-cyclopentyloxy-4-methoxybenzylchloride (10.59 g, 43.98 mmol) were dissolved in acetonitrile (30 ml) in a high pressure vessel and the resulting mixture heated are 120° C. for 24 hours. On cooling to room temperature a solid precipitated from the solution. The solvent was removed in vacuo, cold water (10 ml) and diethyl ether (100 ml) were added to the solid residue, the mixture stirred vigourously and then filtered. The filter cake was washed with ice-cold ethyl acetate (50 ml) and the solid obtained was oven dried in vacuo at 80° C. to give the title compound (9.51 g, 58%) as a slightly off-white solid. The combined filtrates and washings were concentrated in-vacuo, then water (5 ml) and diethyl ether (100 ml) added, and the mixture treated as before to give further title compound (0.718 g, 5%) as a white solid, m.p.=205-207° C. Combined yield 910.23 g, 63%). Tlc, SiO2 (dichloromethane:methanol, 10:1) Rf=0.49, detection U.V., Dragendorff's reagent. the resulting mixture heated precipitated from the solution The solvent was removed in vacuo, cold water (10 ml) and diethyl ether (100 ml) were added to the solid residue filtered The filter cake was washed with ice-cold ethyl acetate (50 ml) the solid obtained dried in vacuo at 80° C.

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

Procedure: 6-ethylamino-8-isopropyl-3H-purine (7.52 g, 36.65 mmol) and 3-cyclopentyloxy-4-methoxybenzylchloride (10.59 g, 43.98 mmol) were dissolved in acetonitrile (30 ml) in a high pressure vessel and the resulting mixture heated are 120° C. for 24 hours. On cooling to room temperature a solid precipitated from the solution. The solvent was removed in vacuo, cold water (10 ml) and diethyl ether (100 ml) were added to the solid residue, the mixture stirred vigourously and then filtered. The filter cake was washed with ice-cold ethyl acetate (50 ml) and the solid obtained was oven dried in vacuo at 80° C. to give the title compound (9.51 g, 58%) as a slightly off-white solid. The combined filtrates and washings were concentrated in-vacuo, then water (5 ml) and diethyl ether (100 ml) added, and the mixture treated as before to give further title compound (0.718 g, 5%) as a white solid, m.p.=205-207° C. Combined yield 910.23 g, 63%). Tlc, SiO2 (dichloromethane:methanol, 10:1) Rf=0.49, detection U.V., Dragendorff's reagent. the resulting mixture heated precipitated from the solution The solvent was removed in vacuo, cold water (10 ml) and diethyl ether (100 ml) were added to the solid residue filtered The filter cake was washed with ice-cold ethyl acetate (50 ml) the solid obtained dried in vacuo at 80° C.

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

Procedure: A mixture of 3-cyclopentyloxy-4-methoxybenzyl chloride (119 g, 0.49 mol), 120 ml of methylene chloride, KCN (70.7 g, 1.09 mol), benzyltriethylammonium chloride (35 g, 0.015 mol) and water (120 ml) was stirred vigorously at room temperature for 48 hours when the reaction was complete by HPLC. The reaction mixture was diluted with methylene chloride and the layers were separated. The methylene chloride solution was extracted several times with water and evaporated to afford 3-cyclopentyloxy-4-methoxyphenylacetonitrile (109 g, 95%) of sufficient purity to be used in the subsequent transformation. the layers were separated The methylene chloride solution was extracted several times with water evaporated

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

Procedure: A solution of 3-cyclopentyloxy-4-methoxybenzyl alcohol (112 g, 0.50 mol) prepared as described above, in 1 liter of methylene chloride was stirred at room temperature with concentrated HCl (110 ml, 1.2 mol) for 3 hours at which time the reaction was done by TLC. The layers were separated and the methylene chloride solution was washed twice with water and evaporated under reduced pressure to give 3-cyclopentyloxy-4-methoxybenzyl chloride (119 g, 100%). The layers were separated the methylene chloride solution was washed twice with water evaporated under reduced pressure