(4R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask cooled to −78° C. under N2 was added 2-butyne gas via syringe needle until approximately ˜3 mL of liquid had condensed in the flask. THF (120 mL) was then added followed by DMPU (18.9 ml, 156 mmol). The flask was purged with N2 and n-butyllithium (2.5M hexanes, 18.7 ml, 46.9 mmol) was added via syringe over 5 min and stirred for an additional 15 min at which time (R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (10.0 g, 39.1 mmol) was added as a solution in THF (30 mL) [preparation of enantiopure (R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane from commercially available (R)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol was performed using the procedure described by: Taber. D. F.; Xu, M.; Hartnett, J. C. J. Am. Chem. Soc. 2002, 124, 13121]. The reaction was slowly warmed to rt and stirred a total of 3 h. The mixture was quenched with sat. NH4Cl, and extracted with Et2O (2×). The organics were washed with H2O, and brine, dried over MgSO4, filtered, and concentrated. The material was purified by silica gel chromatography (5% EtOAc in hexanes gradient to 15% EtOAc in hexanes) to give (R)-4-(hex-3-ynyl)-2,2-dimethyl-1,3-dioxolane as a clear oil. 1H NMR (400 MHz, CDCl3): δ 4.19 (1H, m), 4.08 (1H, dd, J=8.0, 6.0 Hz), 3.58 (1H, dd, J=7.6, 6.8 Hz), 2.26 (2H, m), 2.15 (2H, qt, J=5.2, 2.4 Hz), 1.81 (1H, m), 1.68 (1H, m), 1.40 (3H, s), 1.36 (3H, s), 1.11 (3H, t, J=7.6 Hz). condensed in the flask was added via syringe over 5 min The reaction was slowly warmed to rt The mixture was quenched with sat. NH4Cl extracted with Et2O (2×) The organics were washed with H2O, and brine dried over MgSO4 filtered concentrated The material was purified by silica gel chromatography (5% EtOAc in hexanes gradient to 15% EtOAc in hexanes)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In N,N-dimethylformamide (40 ml) were dissolved 6-methoxypyrido[2,3-b]pyrazin-3(4H)-one (1.48 g, 8.34 mmol) and (4R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (3.20 g, 12.51 mmol). Cesium carbonate (3.81 g, 11.68 mmol) was added to the solution and the mixture was stirred at 50° C. for 13 hours. After cooling in the air, water was added to the reaction solution and the mixture was extracted with ethyl acetate. The extract was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 2.55 g (100%) of the title compound in the form of a light yellow oily product. was added to the reaction solution the mixture was extracted with ethyl acetate The extract was washed with saturated sodium chloride solution dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)

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

Procedure: Triphenyl phosphine (5.94 g, 22.65 mmol) and imidazole (22.65 mmol) were dissolved in a mixed solution (120 ml) of diethyl ether-acetonitrile (3:1). Iodine (5.75 g, 22.65 mmol) was added thereto under cooling on ice and the mixture was stirred at room temperature for 30 minutes. The solution was cooled on ice again, (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane (3.0 mmol, 20.59 mmol) was added thereto and the mixture was stirred at room temperature for 24 hours. A saturated sodium thiosulfate aqueous solution was added to the reaction solution under cooling on ice and stirred for a while, the solution was extracted with diethyl ether and the extract was washed with saturated sodium chloride solution. The solvent was removed under reduced pressure and the residue was purified by silica gel column chromatography (hexane/ethyl acetate) to yield 3.20 g (61%) of the title compound in the form of a yellowish oily product. under cooling on ice The solution was cooled on ice again the mixture was stirred at room temperature for 24 hours under cooling on ice stirred for a while the solution was extracted with diethyl ether the extract was washed with saturated sodium chloride solution The solvent was removed under reduced pressure the residue was purified by silica gel column chromatography (hexane/ethyl acetate)

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a flask cooled to −78° C. under N2 was added 2-butyne gas via syringe needle until approximately ˜3 mL of liquid had condensed in the flask. THF (120 mL) was then added followed by DMPU (18.9 ml, 156 mmol). The flask was purged with N2 and n-butyllithium (2.5M hexanes, 18.7 ml, 46.9 mmol) was added via syringe over 5 min and stirred for an additional 15 min at which time (R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane (10.0 g, 39.1 mmol) was added as a solution in THF (30 mL) [preparation of enantiopure (R)-4-(2-iodoethyl)-2,2-dimethyl-1,3-dioxolane from commercially available (R)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol was performed using the procedure described by: Taber. D. F.; Xu, M.; Hartnett, J. C. J. Am. Chem. Soc. 2002, 124, 13121]. The reaction was slowly warmed to rt and stirred a total of 3 h. The mixture was quenched with sat. NH4Cl, and extracted with Et2O (2×). The organics were washed with H2O, and brine, dried over MgSO4, filtered, and concentrated. The material was purified by silica gel chromatography (5% EtOAc in hexanes gradient to 15% EtOAc in hexanes) to give (R)-4-(hex-3-ynyl)-2,2-dimethyl-1,3-dioxolane as a clear oil. 1H NMR (400 MHz, CDCl3): δ 4.19 (1H, m), 4.08 (1H, dd, J=8.0, 6.0 Hz), 3.58 (1H, dd, J=7.6, 6.8 Hz), 2.26 (2H, m), 2.15 (2H, qt, J=5.2, 2.4 Hz), 1.81 (1H, m), 1.68 (1H, m), 1.40 (3H, s), 1.36 (3H,s), 1.11 (3H, t, J=7.6 Hz). condensed in the flask was added via syringe over 5 min The reaction was slowly warmed to rt The mixture was quenched with sat. NH4Cl extracted with Et2O (2×) The organics were washed with H2O, and brine dried over MgSO4 filtered concentrated The material was purified by silica gel chromatography (5% EtOAc in hexanes gradient to 15% EtOAc in hexanes)