2-(6-chlorohexoxy)oxane

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

Procedure: To a mixture of 15 g of 6-chlorohexanol, 100 ml of methylenechloride and 0.2 g of p-toluenesulphonic acid were added dropwise 12 g of dihydropyrane in 40 ml of methylenechloride. The reaction mixture was stirred for 15 h at room temperature and then distributed between ether and saturated sodium bicarbonate solution. The ether phase was washed with water, dried over sodium sulphate, filtered and concentrated to dryness. Chromatography of the residue on silica using hexane/ether (3:1) gave 21 g of the product as a colourless oil. The ether phase was washed with water dried over sodium sulphate filtered concentrated to dryness

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

Procedure: A mixture of 10 g of 2-(6-chlorohexyloxy)tetrahydropyrane, 25 g of hydroquinone, 31 g of potassiumcarbonate, 0.752 g of potassiumiodide and 250 ml of dimethylsulfoxide was allowed to react for 4 days at 80° C. Subsequently, the reaction mixture was cooled to room temperature and after addition of water extracted with ether. The organic phase was then dried over sodium sulphate, filtered and concentrated to dryness. Chromatography on silica with 10% ethylacetate in toluene gave 11 g of product as a yellowish oil. to react for 4 days at 80° C extracted with ether The organic phase was then dried over sodium sulphate filtered concentrated to dryness

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

Procedure: Sodium (1.13 g, 49 mmol) in small quantities was dissolved in dry ethanol (100 ml) with constant stirring under a blanket of dry nitrogen. Diethyl malonate (8.0 g, 50 mmol) was added in one portion and the solution heated at 60° C. for 1 hour. 2-(6-Chloro-hexyloxy)-tetrahydropyran (9.3 g, 42.2 mmol) was added in one portion and the temperature raised to 75-80° C. and maintained at this level for 24 hours. After cooling, the inorganic solid was removed by filtration and solvent evaporated from the filtrate. The residue was dissolved in CH2Cl2 (50 ml), extracted with water (30 ml×2), dried (MgSO4) filtered and volatiles removed to leave a pale yellow oil. This oil was subject to chromatography on silica gel using pet ether 40:60/ether (200:40) as the eluent. The required product eluted with an rf=0.15 and was isolated as a colourless oil. Yield 8.7 g, (60%). the temperature raised to 75-80° C. maintained at this level for 24 hours After cooling the inorganic solid was removed by filtration and solvent evaporated from the filtrate The residue was dissolved in CH2Cl2 (50 ml) extracted with water (30 ml×2) dried (MgSO4) filtered volatiles removed to leave a pale yellow oil The required product eluted with an rf=0.15 was isolated as a colourless oil

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Chlorohexanol (6.85 g, 10 mmol) and p-toluenesulphonic acid (500 mg), were dissolved in dry ether (75 ml) and cooled to 0-5° C. in an ice bath. Dihydropyran (4.3 g, 10 mmol) in dry ether (25 ml) was added dropwise with constant stirring over a 30 minute period. After complete addition, the cooling bath was removed and stirring continued for 16 hours. The solution was extracted with water (50 ml×2), dried (MgSO4), filtered and the solvent evaporated under reduced pressure to leave a pale yellow oil. This oil was shown by 13C NMR spectroscopy to be sufficiently pure to be used without purification in the subsequent reactions. Yield 10.1 g (91%). After complete addition the cooling bath was removed stirring continued for 16 hours The solution was extracted with water (50 ml×2) dried (MgSO4) filtered the solvent evaporated under reduced pressure to leave a pale yellow oil to be used without purification in the subsequent reactions

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

Procedure: To a mixture of 15 g of 6-chlorohexanol, 100 ml of methylenechloride and 0.2 g of p-toluenesulphonic acid were added dropwise 12 g of dihydropyrane in 40 ml of methylenechloride. The reaction mixture was stirred for 15 h at room temperature and then distributed between ether and saturated sodium bicarbonate solution. The ether phase was washed with water, dried over sodium sulphate, filtered and concentrated to dryness. Chromatography of the residue on silica using hexane/ether (3:1) gave 21 g of the product as a colourless oil. The ether phase was washed with water dried over sodium sulphate filtered concentrated to dryness

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

Procedure: A mixture of 10 g of 2-(6-chlorohexyloxy)tetrahydropyrane, 25 g of hydroquinone, 31 g of potassiumcarbonate, 0.752 g of potassiumiodide and 250 ml of dimethylsulfoxide was allowed to react for 4 days at 80° C. Subsequently, the reaction mixture was cooled to room temperature and after addition of water extracted with ether. The organic phase was then dried over sodium sulphate, filtered and concentrated to dryness. Chromatography on silica with 10% ethylacetate in toluene gave 11 g of product as a yellowish oil. to react for 4 days at 80° C extracted with ether The organic phase was then dried over sodium sulphate filtered concentrated to dryness

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

Procedure: To a mixture of 15 g of 6-chlorohexanol, 100 ml of methylenechloride and 0.2 g of p-toluenesulphonic acid were added dropwise 12 g of dihydropyrane in 40 ml of methylenechloride. The reaction mixture was stirred for 15 h at room temperature and then distributed between ether and saturated sodium bicarbonate solution. The ether phase was washed with water, dried over sodium sulphate, filtered and concentrated to dryness. Chromatography of the residue on silica using hexane/ether (3:1) gave 21 g of the product as a colourless oil. The ether phase was washed with water dried over sodium sulphate filtered concentrated to dryness

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

Procedure: A mixture of 10 g of 2-(6-chlorohexyloxy)tetrahydropyrane, 25 g of hydroquinone, 31 g of potassiumcarbonate, 0.752 g of potassiumiodide and 250 ml of dimethylsulfoxide was allowed to react for 4 days at 80° C. Subsequently, the reaction mixture was cooled to room temperature and after addition of water extracted with ether. The organic phase was then dried over sodium sulphate, filtered and concentrated to dryness. Chromatography on silica with 10% ethylacetate in toluene gave 11 g of product as a yellowish oil. to react for 4 days at 80° C extracted with ether The organic phase was then dried over sodium sulphate filtered concentrated to dryness

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

Procedure: To a solution of 14.3-7g of 6 chloro-1-hexanol and 10.39 g of dihydropyran in 30 ml of methylene chloride was added 0.95 g of tosic acid monohydrate, and the mixture was stirred at room temperature for 18 hours, poured into 50 ml of a saturated sodium bicarbonate aqueous solution, stirred for 10 minutes and extracted three times with 100 ml of chloroform. The extracts were combined, washed with a saturated sodium bicarbonate aqueous solution and a saturated sodium chloride aqueous solution, dried over magnesium sulfate, concentrated under a reduced pressure and dried in vacuo. The orange-colored oil thus obtained was vacuum-distilled to obtain 17.43 g of 2-(6-chlorohexyloxy)tetrahydropyran as a colorless oil. stirred for 10 minutes extracted three times with 100 ml of chloroform washed with a saturated sodium bicarbonate aqueous solution a saturated sodium chloride aqueous solution, dried over magnesium sulfate concentrated under a reduced pressure dried in vacuo The orange-colored oil thus obtained was vacuum-distilled

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Chlorohexanol (6.85 g, 10 mmol) and p-toluenesulphonic acid (500 mg), were dissolved in dry ether (75 ml) and cooled to 0-5° C. in an ice bath. Dihydropyran (4.3 g, 10 mmol) in dry ether (25 ml) was added dropwise with constant stirring over a 30 minute period. After complete addition, the cooling bath was removed and stirring continued for 16 hours. The solution was extracted with water (50 ml×2), dried (MgSO4), filtered and the solvent evaporated under reduced pressure to leave a pale yellow oil. This oil was shown by 13C NMR spectroscopy to be sufficiently pure to be used without purification in the subsequent reactions. Yield 10.1 g (91%). After complete addition the cooling bath was removed stirring continued for 16 hours The solution was extracted with water (50 ml×2) dried (MgSO4) filtered the solvent evaporated under reduced pressure to leave a pale yellow oil to be used without purification in the subsequent reactions

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

Procedure: Sodium (1.13 g, 49 mmol) in small quantities was dissolved in dry ethanol (100 ml) with constant stirring under a blanket of dry nitrogen. Diethyl malonate (8.0 g, 50 mmol) was added in one portion and the solution heated at 60° C. for 1 hour. 2-(6-Chloro-hexyloxy)-tetrahydropyran (9.3 g, 42.2 mmol) was added in one portion and the temperature raised to 75-80° C. and maintained at this level for 24 hours. After cooling, the inorganic solid was removed by filtration and solvent evaporated from the filtrate. The residue was dissolved in CH2Cl2 (50 ml), extracted with water (30 ml×2), dried (MgSO4) filtered and volatiles removed to leave a pale yellow oil. This oil was subject to chromatography on silica gel using pet ether 40:60/ether (200:40) as the eluent. The required product eluted with an rf=0.15 and was isolated as a colourless oil. Yield 8.7 g, (60%). the temperature raised to 75-80° C. maintained at this level for 24 hours After cooling the inorganic solid was removed by filtration and solvent evaporated from the filtrate The residue was dissolved in CH2Cl2 (50 ml) extracted with water (30 ml×2) dried (MgSO4) filtered volatiles removed to leave a pale yellow oil The required product eluted with an rf=0.15 was isolated as a colourless oil

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Chlorohexanol (6.85 g, 10 mmol) and p-toluenesulphonic acid (500 mg), were dissolved in dry ether (75 ml) and cooled to 0-5° C. in an ice bath. Dihydropyran (4.3 g, 10 mmol) in dry ether (25 ml) was added dropwise with constant stirring over a 30 minute period. After complete addition, the cooling bath was removed and stirring continued for 16 hours. The solution was extracted with water (50 ml×2), dried (MgSO4), filtered and the solvent evaporated under reduced pressure to leave a pale yellow oil. This oil was shown by 13C NMR spectroscopy to be sufficiently pure to be used without purification in the subsequent reactions. Yield 10.1 g (91%). After complete addition the cooling bath was removed stirring continued for 16 hours The solution was extracted with water (50 ml×2) dried (MgSO4) filtered the solvent evaporated under reduced pressure to leave a pale yellow oil to be used without purification in the subsequent reactions