butan-2-yl (E)-but-2-enoate

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Several drops of a solution of 4.9 g of n-butyl bromide in 126 ml of dry diethyl ether were added to a suspension of 10.53 g of magnesium and a trace amount of iodine in 80 ml of dry diethyl ether, and the mixture was stirred vigorously. The colour of the iodine disappeared upon slight heating, and the rest of the n-butyl bromide solution was then added dropwise at a rate sufficient to maintain a constant reflux of the reaction mixture. After addition of the n-butyl bromide solution the reaction mixture was heated to reflux for a further 15 minutes and was then cooled to 5° C. with an ice-water bath. Cuprous chloride (0.589 g) was divided into seven equal portions: one portion was added to the reaction mixture and then a solution of 23.9 g of sec-butyl crotonate in 120 ml of dry diethyl ether was added dropwise over 3 hours, during which time the six remaining portions of cuprous chloride were added at 30-minute intervals. After stirring the mixture at 5° C. for 15 minutes and then at room temperature for 1 hour, the reaction mixture was gradually poured into an ice-cooled mixture of 150 g of ice, 50 ml of concentrated hydrochloric acid and 60 ml of diethyl ether with vigorous stirring. The organic layer was separated from the reaction mixture obtained and the aqueous layer was extracted with diethyl ether. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, and then concentrated. The residue was purified by distillation under reduced pressure to give 27.8 g of the title compound having the following physical characteristics: to maintain a constant reflux of the reaction mixture was heated to reflux for a further 15 minutes one portion was added to the reaction mixture were added at 30-minute intervals at room temperature for 1 hour cooled The organic layer was separated from the reaction mixture obtained the aqueous layer was extracted with diethyl ether The organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride, dried over magnesium sulphate concentrated The residue was purified by distillation under reduced pressure

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:0.01; 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:0.01; 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:0.01; 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:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Several drops of a solution of 4.9 g of n-butyl bromide in 126 ml of dry diethyl ether were added to a suspension of 10.53 g of magnesium and a trace amount of iodine in 80 ml of dry diethyl ether, and the mixture was stirred vigorously. The colour of the iodine disappeared upon slight heating, and the rest of the n-butyl bromide solution was then added dropwise at a rate sufficient to maintain a constant reflux of the reaction mixture. After addition of the n-butyl bromide solution the reaction mixture was heated to reflux for a further 15 minutes and was then cooled to 5° C. with an ice-water bath. Cuprous chloride (0.589 g) was divided into seven equal portions: one portion was added to the reaction mixture and then a solution of 23.9 g of sec-butyl crotonate in 120 ml of dry diethyl ether was added dropwise over 3 hours, during which time the six remaining portions of cuprous chloride were added at 30-minute intervals. After stirring the mixture at 5° C. for 15 minutes and then at room temperature for 1 hour, the reaction mixture was gradually poured into an ice-cooled mixture of 150 g of ice, 50 ml of concentrated hydrochloric acid and 60 ml of diethyl ether with vigorous stirring. The organic layer was separated from the reaction mixture obtained and the aqueous layer was extracted with diethyl ether. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium chloride, dried over magnesium sulphate, and then concentrated. The residue was purified by distillation under reduced pressure to give 27.8 g of the title compound having the following physical characteristics: to maintain a constant reflux of the reaction mixture was heated to reflux for a further 15 minutes one portion was added to the reaction mixture were added at 30-minute intervals at room temperature for 1 hour cooled The organic layer was separated from the reaction mixture obtained the aqueous layer was extracted with diethyl ether The organic layer was washed with a saturated aqueous solution of sodium bicarbonate a saturated aqueous solution of sodium chloride, dried over magnesium sulphate concentrated The residue was purified by distillation under reduced pressure

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:0.01; 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