2-cyclopentyloxyethanol

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: To a solution of 2-(cyclopentyloxy)-1-ethanol (prepared as described in J. Org. Chem., 1968, 33, 2271-2284: 127 mg, 0.97 mmol) and triethylamine (101 mg, 0.1 mmol) in dichloromethane (3 mL) at 0° C. was added 4-bromobenzenesulfonyl chloride (255 mg, 0.1 mmol) in dichloromethane (2 mL) dropwise over 5 minutes. The reaction was then warmed to room temperature and stirred for 16 hours. The mixture was then poured into water (3 mL) and the two layers were separated. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a crude residue. This was purified by column chromatography on silica gel (50 g), eluting with a gradient of dichloromethane:hexane (50:50 to 0:100), to give the title compound (200 mg, 59%) as a colourless oil. the two layers were separated The organic layer was dried over sodium sulfate filtered concentrated in vacuo to give a crude residue This was purified by column chromatography on silica gel (50 g) eluting with a gradient of dichloromethane:hexane (50:50 to 0:100)

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

Procedure: To a solution of 2-(cyclopentyloxy)-1-ethanol (prepared as described in J. Org. Chem., 1968, 33, 2271-2284: 127 mg, 0.97 mmol) and triethylamine (101 mg, 0.1 mmol) in dichloromethane (3 mL) at 0° C. was added 4-bromobenzenesulfonyl chloride (255 mg, 0.1 mmol) in dichloromethane (2 mL) dropwise over 5 minutes. The reaction was then warmed to room temperature and stirred for 16 hours. The mixture was then poured into water (3 mL) and the two layers were separated. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a crude residue. This was purified by column chromatography on silica gel (50 g), eluting with a gradient of dichloromethane:hexane (50:50 to 0:100), to give the title compound (200 mg, 59%) as a colourless oil. the two layers were separated The organic layer was dried over sodium sulfate filtered concentrated in vacuo to give a crude residue This was purified by column chromatography on silica gel (50 g) eluting with a gradient of dichloromethane:hexane (50:50 to 0:100)

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

Procedure: 2-Cyclopentyloxyethanol (4.3 g, 33.1 mmol) in pyridine (18 ml) was added dropwise to a solution of 3-toluenesulphonyl chloride (6.8 g, 35.7 mmol) in pyridine (27 ml) at 5° C. The mixture was allowed to warm to ambient temperature, and stirred overnight. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) and the product was extracted with ether. The organic phase was washed with 2M hydrochloric acid, dried (MgSO4) and the solvent removed by evaporation to give 2-cyclopentyloxyethyl 4-toluenesulphonate (6.9 g, 73%) which was used without further purification. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) the product was extracted with ether The organic phase was washed with 2M hydrochloric acid dried (MgSO4) the solvent removed by evaporation

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

Procedure: 2-Cyclopentyloxyethanol (4.3 g, 33.1 mmol) in pyridine (18 ml) was added dropwise to a solution of 3-toluenesulphonyl chloride (6.8 g, 35.7 mmol) in pyridine (27 ml) at 5° C. The mixture was allowed to warm to ambient temperature, and stirred overnight. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) and the product was extracted with ether. The organic phase was washed with 2M hydrochloric acid, dried (MgSO4) and the solvent removed by evaporation to give 2-cyclopentyloxyethyl 4-toluenesulphonate (6.9 g, 73%) which was used without further purification. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) the product was extracted with ether The organic phase was washed with 2M hydrochloric acid dried (MgSO4) the solvent removed by evaporation

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 g (2.32 mols) of cyclopentanol, 38.5 cc (0.77 mol) of ethylene oxide and 2.3 g (0.1 g atom) of sodium metal are introduced at 0° C. into a 500 ml autoclave. The mixture is then heated for 4 hours at 75° C. The autoclave is left to cool and the reaction mixture is then distilled. This gives the title compound, which boils at 90°-92° C. under a pressure of 15 mm Hg. The autoclave is left to cool the reaction mixture is then distilled

Conditions: temp:75.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 200 g (2.32 mols) of cyclopentanol, 38.5 cc (0.77 mol) of ethylene oxide and 2.3 g (0.1 g atom) of sodium metal are introduced at 0° C. into a 500 ml autoclave. The mixture is then heated for 4 hours at 75° C. The autoclave is left to cool and the reaction mixture is then distilled. This gives the title compound, which boils at 90°-92° C. under a pressure of 15 mm Hg. The autoclave is left to cool the reaction mixture is then distilled

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

Procedure: 1,1-(Azodicarbonyl)dipiperidine (355 mg, 1.4 mmol) was added in portions to a mixture of 44-chloro-2-fluoroanilino)-7-hydroxy-methoxyquinazoline (I 50 mg, 0.47 mmol), (prepared as described for the starting material in Example 2), 2-(cyclopentyloxy)ethanol (91 mg, 0.7 mmol), (U.S. Pat. No. 4,515,814), and tributylphosphine (284 mg, 1.4 mmol) in methylene chloride (6 ml) at 0° C. The mixture was then allowed to warm to ambient temperature and stirred for 3.5 hours. Ether (3 ml) was added and the insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was dissolved in acetone and 1M ethereal hydrogen chloride (0.6 ml) was added. The mixture was left to stand for 60 hours and the precipitate was collected by filtration, washed with acetone and dried to give 44-chloro-2-fluoroanilino)-72-cyclopentyl xyethoxy)-4-methoxyquinazoline hydrochloride (130 mg, 60%). (prepared at 0° C the insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was dissolved in acetone 1M ethereal hydrogen chloride (0.6 ml) was added The mixture was left to stand for 60 hours the precipitate was collected by filtration washed with acetone dried

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

Procedure: 1,1′-(Azodicarbonyl)dipiperidine (355 mg, 1.4 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (150 mg, 0.47 mmol), (prepared as described for the starting material in Example 2), 2-(cyclopentyloxy)ethanol (91 mg, 0.7 mmol), (U.S. Pat. No. 4,515,814), and tributylphosphine (284 mg, 1.4 mmol) in methylene chloride (6 ml) at 0° C. The mixture was then allowed to warm to ambient temperature and stirred for 3.5 hours. Ether (3 ml) was added and the insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was dissolved in acetone and 1M ethereal hydrogen chloride (0.6 ml) was added. The mixture was left to stand for 60 hours and the precipitate was collected by filtration, washed with acetone and dried to give 4-(4-chloro-2-fluoroanilino)-7-(2-cyclopentyloxyethoxy)-6-methoxyquinazoline hydrochloride (130 mg, 60%). (prepared at 0° C the insolubles were removed by filtration the volatiles were removed from the filtrate by evaporation The residue was dissolved in acetone 1M ethereal hydrogen chloride (0.6 ml) was added The mixture was left to stand for 60 hours the precipitate was collected by filtration washed with acetone dried

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

Procedure: To a solution of 2-(cyclopentyloxy)-1-ethanol (prepared as described in J. Org. Chem., 1968, 33, 2271-2284: 127 mg, 0.97 mmol) and triethylamine (101 mg, 0.1 mmol) in dichloromethane (3 mL) at 0° C. was added 4-bromobenzenesulfonyl chloride (255 mg, 0.1 mmol) in dichloromethane (2 mL) dropwise over 5 minutes. The reaction was then warmed to room temperature and stirred for 16 hours. The mixture was then poured into water (3 mL) and the two layers were separated. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a crude residue. This was purified by column chromatography on silica gel (50 g), eluting with a gradient of dichloromethane:hexane (50:50 to 0:100), to give the title compound (200 mg, 59%) as a colourless oil. the two layers were separated The organic layer was dried over sodium sulfate filtered concentrated in vacuo to give a crude residue This was purified by column chromatography on silica gel (50 g) eluting with a gradient of dichloromethane:hexane (50:50 to 0:100)

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

Procedure: 2-Cyclopentyloxyethanol (4.3 g, 33.1 mmol) in pyridine (18 ml) was added dropwise to a solution of 3-toluenesulphonyl chloride (6.8 g, 35.7 mmol) in pyridine (27 ml) at 5° C. The mixture was allowed to warm to ambient temperature, and stirred overnight. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) and the product was extracted with ether. The organic phase was washed with 2M hydrochloric acid, dried (MgSO4) and the solvent removed by evaporation to give 2-cyclopentyloxyethyl 4-toluenesulphonate (6.9 g, 73%) which was used without further purification. The mixture was poured onto ice containing concentrated hydrochloric acid (46 ml) the product was extracted with ether The organic phase was washed with 2M hydrochloric acid dried (MgSO4) the solvent removed by evaporation