1,4-dioxaspiro[4.5]decane

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

実験手順: To the slurry of zirconium tetrachloride (10.65 g, 45.7 mmol) in THF (100 mL) was added sodium borohydride (4.3 g, 114.3 mmol) in small portions at room temperature. A solution of 1,4-dioxaspiro[4.5]decane (6.5 g, 45.7 mmol) in THF (20 mL) was added dropwise and the resulting mixture was stirred at room temperature overnight. The reaction was carefully quenched with 1N HCl and extracted with ethyl acetate. The organic phase was washed with brine, dried and concentrated to give a crude product, which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (3:2) to give 2-(cyclohexyloxy)ethanol (3.9 g, 59.2% yield) as light yellow oil. 1H-NMR (CDCl3) δ 3.68-3.70 (t, 2H), 3.53-3.56 (m, 2H), 3.27-3.29 (m, 1H), 2.54 (br, 1H), 1.89-1.93 (m, 2H), 1.70-1.73 (m, 2H), 1.51-1.54 (m, 1H), 1.17-1.28 (m, 5H). The reaction was carefully quenched with 1N HCl extracted with ethyl acetate The organic phase was washed with brine dried concentrated to give a crude product, which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (3:2)

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

実験手順: To a solution of cyclohexanone (10 g, 0.102 mol) in ethylene glycol (50 mL) was added iodine (3.88 g, 15.3 mmol) and the resulting mixture was stirred at room temperature overnight. The mixture was diluted with ethyl acetate and extracted with saturated aqueous sodium thiosulfate. The organic phase was dried and concentrated to give a crude product, which was purified via silica gel chromatography eluting with ethyl acetate/petroleum ether (1:8) to give 1,4-dioxaspiro[4.5]decane (6.8 g, 46.9% yield) as light oil. 1H-NMR (CDCl3) δ 3.93(s, 4H), 1.58-1.59 (d, 8H), 1.39-1.41(m, 2H). extracted with saturated aqueous sodium thiosulfate The organic phase was dried concentrated to give a crude product, which was purified via silica gel chromatography eluting with ethyl acetate/petroleum ether (1:8)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At 50° C. 16.0 g potassium carbonate and 20.0 g of 8-methanesulphonyloxy-(1,4-dioxa-spiro[4,5]decan are added to 20.0 g 3-benzyl-3,4-dihydro-4-oxo-6-hydroxy-7-methoxy-quinazoline in 150 ml N,N-dimethylformamide and the mixture is vigorously stirred for 18 hours at 80° C. To complete the reaction potassium carbonate and 8-methanesulphonyloxy-(1,4-dioxa-spiro[4,5]decane are each added three times more and in each case the mixture is stirred for several hours at 80° C. The reaction mixture is cooled and slowly combined with a total of 500 ml of water. The precipitate is suction filtered, washed with water and dried. At 50° C each added three times more in each case the mixture is stirred for several hours at 80° C The reaction mixture is cooled filtered washed with water dried

反応条件: temp:-100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At −100° C., 22 g of 1,1-difluoroethylene were condensed into a solvent mixture of 400 ml of tetrahydrofuran and 100 ml of diethyl ether. Subsequently, 153 ml of a 1.3 molar solution of sec-BuLi were added dropwise to the reaction solution at a temperature between −90° C. and −100° C. Finally, 31.2 g of 1,4-dioxaspiro[4.5]decane were added, the solution was stirred at −100° C. for another 20 minutes and subsequently warmed to 0° C. with stirring. The reaction solution was poured into an aqueous ammonium chloride and extracted with methylene chloride and the combined organic phases were dried over magnesium sulfate and concentrated. The residue was taken up in 400 ml of methylene chloride and, at −70° C., reacted with 32 g (0.2 mol) of DAST, dissolved in 100 ml of methylene chloride. The mixture was then slowly warmed to 0° C. with stirring, and the reaction solution was subsequently poured into an aqueous ammonium chloride. The product was extracted with diethyl ether and the combined organic phases were dried over MgSO4 and concentrated. The residue was chromatographed over silica gel (petroleum ether/ethyl acetate 4:1), to give the title product as a colourless oil. At −100° C. condensed subsequently warmed to 0° C. with stirring extracted with methylene chloride the combined organic phases were dried over magnesium sulfate concentrated was taken up in 400 ml of methylene chloride and, at −70° C. The mixture was then slowly warmed to 0° C. with stirring The product was extracted with diethyl ether the combined organic phases were dried over MgSO4 concentrated The residue was chromatographed over silica gel (petroleum ether/ethyl acetate 4:1)

反応条件: temp:-60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At −100° C., 17.2 g of chlorotrifluoroethylene were condensed into 120 ml of tetrahydrofuran and 80 ml of diethyl ether. Over a period of 30 minutes, 84 ml of a 16 molar solution of n-BuLi in hexane were added dropwise at a temperature between −90° C. and −100° C. 18.8 g of 1,4-dioxaspiro[4.5]decane were added and the mixture was stirred at −60° C. for 1 h. The reaction solution was poured into aqueous ammonium chloride and extracted with diethyl ether and the combined organic phases were dried over magnesium sulfate and concentrated. The residue was taken up in 200 ml of pyrimidine and, at −30° C., mixed with 71 g of thionyl chloride. The reaction solution was slowly warmed to 0° C. and stirred for another 1.5 hours at this temperature. The reaction solution was poured onto ice and extracted with methylene chloride and the organic phase was dried over magnesium sulfate and concentrated. The residue was chromatographed over silica gel (petroleum ether:ethyl acetate 4:1), to give the title product as a yellow oil. At −100° C. extracted with diethyl ether the combined organic phases were dried over magnesium sulfate concentrated was taken up in 200 ml of pyrimidine and, at −30° C. mixed with 71 g of thionyl chloride The reaction solution was slowly warmed to 0° C. stirred for another 1.5 hours at this temperature The reaction solution was poured onto ice extracted with methylene chloride the organic phase was dried over magnesium sulfate concentrated The residue was chromatographed over silica gel (petroleum ether:ethyl acetate 4:1)

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

実験手順: 2-(2-Cyanopropyl)-4-(4-methoxybenzyl)cyclohexanone 1,4-Dioxospiro[4,5]decan-8-one (45.6 g) was added to a mixture of 4-methoxybenzyl triphenylphosphonium bromide (127.3 g) and epichlorohydrin (100 ml) in toluene (1500 ml) and heated at reflux under a nitrogen atmosphere for 36 hours. The solvent was evaporated under reduced pressure and the residue was extracted into hexane. The hexane solution was evaporated under reduced pressure and the residue distilled at 24° C./1 mmHg to give 8-(4-methoxybenzylidine)- 1,4-dioxaspiro[4,5]-decane, (19 g). heated at reflux under a nitrogen atmosphere for 36 hours The solvent was evaporated under reduced pressure the residue was extracted into hexane The hexane solution was evaporated under reduced pressure the residue distilled at 24° C./1 mmHg