2-(2-bromopropyl)-1,3-dioxolane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Crotonaldehyde (9.18 g, 108 mmol) was added dropwise to a stirring solution of bromotrimethylsilane (24 g, 156 mmol) at 0° C., stirred for 1 hour at 0° C. then warmed to room temperature and stirred for a further 1 hour. Ethylene glycol (9.5 g, 156 mmol) and p-tolunesulphonic acid (100 mg) was added and the solution was heated to reflux, water was removed by use of Dean and Stark apparatus. On completion the mixture was cooled to room temperature and washed with aqueous sodiumhydrogen carbonate solution (saturated, 2×50 ml). The residue was purified by vacuum distillation to give 2-(2-bromopropyl)-1,3-dioxolane (18.8 g, 40-42° C. @ 1 mm Hg, 89%) then warmed to room temperature stirred for a further 1 hour the solution was heated to reflux water was removed by use of Dean and Stark apparatus On completion the mixture was cooled to room temperature washed with aqueous sodiumhydrogen carbonate solution (saturated, 2×50 ml) The residue was purified by vacuum distillation

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring suspension of activated “Rieke” zinc in tetrahydrofuran (21 ml, 1.53 M) was added 2-(2-bromopropyl)-1,3-dioxolane (6.6 g) in tetrahydrofuran (50 ml), a rise in temperature from 21° C. to 40° C. was observed, heated at 40° C. for 1 hour then allowed to cool to ambient temperature before adding 2-chloro-5-fluoropyrimidine (3 g) and [1,2-Bis(diphenylphosphino)-propane]dichloronickel(II) chloride (368 mg). The mixture was stirred at ambient temperature for 4 hours then filtered through a pad of celite and the filtrate evaporated under reduced pressure. Flash chromatography (silica gel, haxane-25% ethyl acetate in hexanes) then gave the product as a pale yellow oil (1.1 g); 1H NMR (d6-DMSO): 8.81 (s, 2H), 4.73 (dd, 1H), 3.66-3.87 (m, 4H), 3.21-3.30 (m, 1H), 2.19 (ddd, 1H), 1.83 (ddd, 1H), 1.27 (d, 3H); m/z 213 (M+1). To a stirring suspension from 21° C. to 40° C. to cool to ambient temperature then filtered through a pad of celite the filtrate evaporated under reduced pressure

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Crotonaldehyde (9.18 g, 108 mmol) was added dropwise to a stirring solution of bromotrimethylsilane (24 g, 156 mmol) at 0° C., stirred for 1 hour at 0° C. then warmed to room temperature and stirred for a further 1 hour. Ethylene glycol (9.5 g, 156 mmol) and p-tolunesulphonic acid (100 mg) was added and the solution was heated to reflux, water was removed by use of Dean and Stark apparatus. On completion the mixture was cooled to room temperature and washed with aqueous sodiumhydrogen carbonate solution (saturated, 2×50 ml).The residue was purified by vacuum distillation to give 2-(2-bromopropyl)-1,3-dioxolane (18.8 g, 40–42° C. @1 mm Hg, 89%) then warmed to room temperature stirred for a further 1 hour the solution was heated to reflux water was removed by use of Dean and Stark apparatus On completion the mixture was cooled to room temperature washed with aqueous sodiumhydrogen carbonate solution (saturated, 2×50 ml).The residue was purified by vacuum distillation

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirring suspension of activated “Rieke” zinc in tetrahydrofuran (21 ml, 1.53M) was added 2-(2-bromopropyl)-1,3-dioxolane (6.6 g) in tetrahydrofuran (50 ml), a rise in temperature from 21° C. to 40° C. was observed, heated at 40° C. for 1 hour then allowed to cool to ambient temperature before adding 2-chloro-5-fluoropyrimidine (3 g) and [1,2-Bis(diphenylphosphino)-propane]dichloronickel(II)chloride (368 mg). The mixture was stirred at ambient temperature for 4 hours then filtered through a pad of celite and the filtrate evaporated under reduced pressure. Flash chromatography (silica gel, haxane-25% ethyl acetate in hexanes) then gave the product as a pale yellow oil (1.1 g); 1H NMR (d6-DMSO): 8.81 (s, 2H), 4.73 (dd, 1H), 3.66–3.87 (m, 4H), 3.21–3.30 (m, 1H), 2.19 (ddd, 1H), 1.83 (ddd, 1H), 1.27(d, 3H); m/z 213 (M+1). To a stirring suspension from 21° C. to 40° C. to cool to ambient temperature then filtered through a pad of celite the filtrate evaporated under reduced pressure