2-(5-bromopentoxy)oxane

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: Three drops of phosphoryl chloride were added to a stirred mixture of 5-bromopentanol (34.3 g, 205 mmol) and dihydropyran (19.0 g, 226 mmol). After standing for one hour, the mixture was fractionated. Yield 34.7 g, b.p. 102° C. (0.2 bar). Chromatography on alumina eluted with petroleum ether gave the pure title compound (25.1 g, 52% of theory) as an oil. Chromatography on alumina eluted with petroleum ether

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

Procedure: A solution of diisopropylamine (1.78 mL) in dry THF (10 mL) at 0° C. under nitrogen was treated dropwise with n-butyl lithium (2.5M in hexanes, 5.09 mL) to generate a pale yellow solution which was stirred at 0° C. for 30 minutes then cooled to −78° C. and treated dropwise with ethyl isobutyrate (1.55 mL). The solution was stirred at −78° C. for 45 minutes then a solution of 2-(5-bromopentyloxy)tetrahydro-2H-pyran (example 285, step a) (3.20 g) in dry THF (1 mL) was added dropwise. The reaction mixture was stirred at −78° C. for 10 minutes then was allowed to warn to room temperature overnight. The reaction mixture was cooled to 0° C. then treated with saturated aqueous ammonium chloride solution (3 mL) and extracted with ethyl acetate. The aqueous phase was extracted with ethyl acetate (×2) and the combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine then dried over sodium sulfate, filtered and evaporated. Purification was by silica gel chromatography eluting with 0-5% ethyl acetate in cyclohexane to afford the subtitled compound as colourless liquid. Yield 2.22 g. then cooled to −78° C. The solution was stirred at −78° C. for 45 minutes The reaction mixture was stirred at −78° C. for 10 minutes to warn to room temperature overnight The reaction mixture was cooled to 0° C. extracted with ethyl acetate The aqueous phase was extracted with ethyl acetate (×2) the combined organic phase was washed with water, saturated aqueous sodium bicarbonate solution and brine then dried over sodium sulfate filtered evaporated Purification eluting with 0-5% ethyl acetate in cyclohexane

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

Procedure: To a solution of 5-bromopentanol (10 g) in DCM (150 mL) was added pyridinium p-toluenesulfonate (1.5 g) followed by 3,4-dihydro-2H-pyran (8.1 mL) and the reaction mixture was stirred at room temperature under nitrogen for 21 hours. The solution was diluted with ether then washed with diluted brine (1:1 brine:water, 140 mL) before the organics were dried over sodium sulfate, filtered and evaporated. Purification was by silica gel chromatography eluting with 0 to 50% ethyl acetate in cyclohexane to afford the subtitled compound as a colourless liquid. Yield 14.14 g. then washed with diluted brine (1:1 brine:water, 140 mL) before the organics were dried over sodium sulfate filtered evaporated Purification eluting with 0 to 50% ethyl acetate in cyclohexane

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

Procedure: Three drops of phosphoryl chloride were added to a stirred mixture of 5-bromopentanol (34.3 g, 205 mmol) and dihydropyran (19.0 g, 226 mmol). After standing for one hour, the mixture was fractionated. Yield 34.7 g, b.p. 102° C. (0.2 bar). Chromatography on alumina eluted with petroleum ether gave the pure title compound (25.1 g, 52% of theory) as an oil. Chromatography on alumina eluted with petroleum ether

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

Procedure: Three drops of phosphoryl chloride were added to a stirred mixture of 5-bromopentanol (34.3 g, 205 mmol) and dihydropyran (19.0 g, 226 mmol). After standing for one hour, the mixture was fractionated. Yield 34.7 g, b.p. 102° C. (0.2 bar). Chromatography on alumina eluted with petroleum ether gave the pure title compound (25.1 g, 52% of theory) as an oil. Chromatography on alumina eluted with petroleum ether

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

Procedure: Under an atmosphere of nitrogen, a mixture of 250 mg of magnesium, 2.8 g of 5-bromo-1-(tetrahydropyran-2-yloxy)pentane, 200 μl of ethyl bromide, a trace amount of iodine and 4 ml of tetrahydrofuran was refluxed with heating for one hour. To it were added 516 mg of crotonic acid sec-butyl ester and 14 mg of cuprous chloride at 0° C. over a period of 30 minutes, the mixture stirred at 0° C. for 15 minutes, and then at room temperature for one hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, the extract washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent to give 529 mg of the subtitle compound having the following physical characteristics: with heating for one hour at room temperature for one hour extracted with ethyl acetate the extract washed with a saturated aqueous solution of sodium chloride dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent

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

Procedure: To 36 g of 5-bromopentan-1-ol were added 24.72 ml of 2,3-dihydropyran and 3 drops of phosphorus oxychloride under cooling in an ice bath, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with diethyl ether, washed with 5% aqueous potassium hydroxide, water, a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:19) as eluent to give 49.5 g of the subtitle compound having the following physical characteristics: under cooling in an ice bath washed with 5% aqueous potassium hydroxide, water a saturated aqueous solution of sodium chloride, dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:19) as eluent

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

Procedure: Under an atmosphere of nitrogen, a mixture of 250 mg of magnesium, 2.8 g of 5-bromo-1-(tetrahydropyran-2-yloxy)pentane, 200 μl of ethyl bromide, a trace amount of iodine and 4 ml of tetrahydrofuran was refluxed with heating for one hour. To it were added 516 mg of crotonic acid sec-butyl ester and 14 mg of cuprous chloride at 0° C. over a period of 30 minutes, the mixture stirred at 0° C. for 15 minutes, and then at room temperature for one hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, the extract washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent to give 529 mg of the subtitle compound having the following physical characteristics: with heating for one hour at room temperature for one hour extracted with ethyl acetate the extract washed with a saturated aqueous solution of sodium chloride dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent

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

Procedure: To 36 g of 5-bromopentan-1-ol were added 24.72 ml of 2,3-dihydropyran and 3 drops of phosphorus oxychloride under cooling in an ice bath, and the mixture was stirred overnight at room temperature. The reaction mixture was diluted with diethyl ether, washed with 5% aqueous potassium hydroxide, water, a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:19) as eluent to give 49.5 g of the subtitle compound having the following physical characteristics: under cooling in an ice bath washed with 5% aqueous potassium hydroxide, water a saturated aqueous solution of sodium chloride, dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of ethyl acetate and hexane (1:19) as eluent

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

Procedure: Under an atmosphere of nitrogen, a mixture of 250 mg of magnesium, 2.8 g of 5-bromo-1-(tetrahydropyran-2-yloxy)pentane, 200 μl of ethyl bromide, a trace amount of iodine and 4 ml of tetrahydrofuran was refluxed with heating for one hour. To it were added 516 mg of crotonic acid sec-butyl ester and 14 mg of cuprous chloride at 0° C. over a period of 30 minutes, the mixture stirred at 0° C. for 15 minutes, and then at room temperature for one hour. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, the extract washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulphate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent to give 529 mg of the subtitle compound having the following physical characteristics: with heating for one hour at room temperature for one hour extracted with ethyl acetate the extract washed with a saturated aqueous solution of sodium chloride dried over magnesium sulphate concentrated under reduced pressure The residue was purified by column chromatography on silica gel using a mixture of methylene chloride and ethyl acetate (20:1) as eluent