hexa-1,5-diene

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 13.70 g (32.60 mmol) of crude 10-(N-benzyloxycarbonylamino)-2-formylamino-3-hydroxy-4-methylene-decanoic acid ethyl ester in 137 ml of tetrahydrofuran there are added, under argon, 18.5 ml (156.4 mmol) of hexa-1,5-diene and then, dropwise at 10° within a period of 15 minutes, 6.1 ml (78.2 mmol) of thionyl bromide. The mixture is stirred for one hour at 10° and for 2 hours at room temperature and is then poured into 200 ml of ice-cold saturated sodium hydrogen carbonate solution; the organic phase is separated off and re-extracted once with dichloromethane. The organic phases are washed with ice-cold 0.5-normal sodium hydrogen carbonate solution and then with saturated sodium chloride solution, dried over sodium sulfate and concentrated to dryness by evaporation in vacuo at 40°. 64 ml (260 mmol) of triisopropyl phosphite (96%) are added immediately to the resulting crude 10-(N-benzyloxycarbonylamino)-4-bromomethyl-2-formylamino-dec-3-enoic acid ethyl ester (27 g, yellow honey), and the mixture is stirred for 17 hours at 80° under a pressure of approximately 100 mbar, the isopropyl bromide that forms being captured in a cold trap (CO2). The excess triisopropyl phosphite is then distilled off under reduced pressure and the evaporation residue (23 g) is purified by chromatography on a column filled with 650 mg of silica gel (0.04-0.063 mm) with ethyl acetate/methanol (95:5). 8.73 g of 10-(N-benzyloxycarbonylamino)-4-diisopropylphosphonomethyl-2-formylaminodec-3-enoic acid ethyl ester are obtained in the form of a yellowish honey. the organic phase is separated off re-extracted once with dichloromethane The organic phases are washed with ice-cold 0.5-normal sodium hydrogen carbonate solution with saturated sodium chloride solution, dried over sodium sulfate concentrated to dryness by evaporation in vacuo at 40° the mixture is stirred for 17 hours at 80° under a pressure of approximately 100 mbar The excess triisopropyl phosphite is then distilled off under reduced pressure the evaporation residue (23 g) is purified by chromatography on a column filled with 650 mg of silica gel (0.04-0.063 mm) with ethyl acetate/methanol (95:5)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2.46 g (6.5 mmol) of 8-(N-benzyloxycarbonylamino)-2-formylamino-3-hydroxy-4-methylene-octanoic acid methyl ester in 25 ml of tetrahydrofuran there are added 5.5 ml (46 mmol) of hexa-1,5-diene and then, dropwise at -50°, 2.6 ml (32.5 mmol) of thionyl bromide. The mixture is stirred at from 0° to 5° for 2 hours, poured into 25 ml of ice-cold saturated sodium hydrogen carbonate solution and extracted twice with 20 ml of methylene chloride each time. The organic phase is washed with 10 ml of saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness by evaporation. The resulting oil is purified by chromatography on silica gel with hexane/ethyl acetate (3:1). 8-(N-benzyloxycarbonylamino)-4-bromomethyl-2-formylamino-oct-3-enoic acid methyl ester is obtained. dropwise at -50° extracted twice with 20 ml of methylene chloride each time The organic phase is washed with 10 ml of saturated sodium chloride solution dried over magnesium sulfate concentrated to dryness by evaporation The resulting oil is purified by chromatography on silica gel with hexane/ethyl acetate (3:1)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the same apparatus and procedures as EXAMPLE 1, 37.5 g (0.153 mole) of 3-(ethylphenyl)-1,1-dichloro-1-silabutane and 100 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 5 g (0.061 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 24.6 g (190°-192° C./0.03 mmHg) of bis[{2-(ethylphenyl)propyl}dichlorosilyl]hexane in 69.8% yield. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere Vacuum distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the same apparatus and procedures as EXAMPLE 1, 37.5 g (0.153 mole) of 3-(ethylphenyl)-1,1-dichloro-1-silabutane and 100 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 5 g (0.061 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 24.6 g (190°-192° C./0.03 mmHg) of bis[{2-(ethylphenyl)propyl}dichlorosilyl]hexane in 69.8% yield. The solution was reacted for 14 hours at reflux under the dry nitrogen atmosphere Vacuum distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the same apparatus and procedures as EXAMPLE 1, 21.3 g (0.097 mole) of 3-(phenyl)-1,1-dichloro-1-silabutane and 100 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 3.2 g (0.039 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 15 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 13.4 g (185°-187° C./0.03 mmHg) of bis{(2-phenylpropyl)dichlorosilyl}hexane in 66.0% yield. The solution was reacted for 15 hours at reflux under the dry nitrogen atmosphere Vacuum distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In the same apparatus and procedures as EXAMPLE 1, 21.3 g (0.097 mole) of 3-(phenyl)-1,1-dichloro-1-silabutane and 100 μl of 1% chloroplatinic acid solution in isopropanol were placed and then 3.2 g (0.039 mole) of 1,5-hexadiene was added dropwise for 5 min. The solution was reacted for 15 hours at reflux under the dry nitrogen atmosphere. Vacuum distillation gave 13.4 g (185°-187° C./0.03 mmHg) of bis{(2-phenylpropyl)dichlorosilyl}hexane in 66.0% yield. The solution was reacted for 15 hours at reflux under the dry nitrogen atmosphere Vacuum distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1 mmol 1-(1-benzyl-piperidin-4-yl)-4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine dissolved in EtOH (10 mL) was added 1 mmol 8-oxa-3-aza-bicyclo[3.2.1]octane, (Newth, F. H. and Wiggins, L. F. Journal of the Chemical Society. 1948, pages 155-158) prepared from 1,5-hexadiene by the four-step process of RuCl3-catalyzed NaIO4 oxidation, conversion to the bis tosylate, cyclization with benzyl amine, and deprotection with 1-chloroethyl chloroformate followed by methanol (Scheme 46). The reaction was stirred for 18 h. The solvents were evaporated and the reminder was triturated with diethyl ether/hexane. The solid was filtered off and washed with hexane. Drying on the fritted funnel provided a solid. The solvents were evaporated the reminder was triturated with diethyl ether/hexane The solid was filtered off washed with hexane Drying on the fritted funnel provided a solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 1 mmol 1-(1-benzyl-piperidin-4-yl)-4,6-dichloro-1H-pyrazolo[3,4-d]pyrimidine dissolved in EtOH (10 mL) was added 1 mmol 8-oxa-3-aza-bicyclo[3.2.1]octane, (Newth, F. H. and Wiggins, L. F. Journal of the Chemical Society. 1948, pages 155-158) prepared from 1,5-hexadiene by the four-step process of RuCl3-catalyzed NaIO4 oxidation, conversion to the bis tosylate, cyclization with benzyl amine, and deprotection with 1-chloroethyl chloroformate followed by methanol (Scheme 46). The reaction was stirred for 18 h. The solvents were evaporated and the reminder was triturated with diethyl ether/hexane. The solid was filtered off and washed with hexane. Drying on the fritted funnel provided a solid. The solvents were evaporated the reminder was triturated with diethyl ether/hexane The solid was filtered off washed with hexane Drying on the fritted funnel provided a solid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Butanol solution of chloroplatinic acid was added to 41.1 g of 1,5-hexadiene, and to this mixture, 106.2 g of dimethoxymethylsilane was gradually added dropwise. Due to the exothermic nature of the reaction, the speed of the dropwise addition was adjusted so that temperature of the reaction mixture was up to 80° C. After the completion of the dropwise addition, the mixture was distilled at reduced pressure under clean conditions as in the case of Synthetic Example 1 to obtain 1,5-bis(dimethoxymethylsilyl)hexane. Due to the exothermic nature of the reaction the speed of the dropwise addition was up to 80° C After the completion of the dropwise addition the mixture was distilled at reduced pressure under clean conditions as in the case of Synthetic Example 1

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Acetoxylation of l'hexa-1,5-diene ##STR3## A 500 ml three-neck flask is charged with 15 g of hexa-1,5-diene (0.18 moles), 150 g of acetic acid, 0.77 g of benzoquinone (7 mmoles), 1 g of charcoal and 80 mg of palladium acetate (0.35 mmoles). The temperature is taken to 50°, then 7 g (0.14 moles) of 70% by weight hydrogen peroxide are introduced in 8 h, and the reaction is allowed to proceed for a further 2 h while maintaining the temperature at 50°. The acetic acid is then distilled (35°, 20×102Pa). The residue is distilled under vacuum to provide 1-acetoxy-3-methylene-cyclopentane in 65% molar yield. 1-acetoxy-3-methylene-cyclopentane is taken to 50° while maintaining the temperature at 50° The acetic acid is then distilled (35°, 20×102Pa) The residue is distilled under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 5.0 g of 2-formylamino-3-hydroxy-4-methylene-6-heptenoic acid methyl ester in 200 ml of dry tetrahydrofuran are cooled to -78°, and 20 ml of 1,5-hexadiene are added thereto. 9 ml of thionyl bromide are added slowly dropwise in such a manner that the reaction temperature does not exceed -50°. When the addition is complete, the reaction solution is heated to 0° within a period of approximately 3 hours and is stirred at that temperature for 3 hours. The solution is then poured onto 300 ml of a cold (5°-10°) saturated sodium bicarbonate solution and extracted with diethyl ether. The organic extracts are washedwith saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation in vacuo. Purification by column chromatography (silica gel, ethyl acetate/hexane 1:1) yields E-2-formylamino-4-bromomethyl-3,6-heptadienoic acid methyl ester in the form of a colourless oil, 1H-NMR (CDCl3): 3.20 (d, 2H, C(5 )--H); 4.00 (s, 2H, CH2Br). does not exceed -50° When the addition the reaction solution is heated to 0° within a period of approximately 3 hours extracted with diethyl ether dried over magnesium sulphate concentrated by evaporation in vacuo Purification by column chromatography (silica gel, ethyl acetate/hexane 1:1)