1-溴-4-(2-甲氧基乙氧基)丁烷

反应条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A 5 L 3-neck round bottom flask was fitted with a thermocouple probe, a 2 L dropping funnel, an inlet argon, and a mechanical stirrer. After the addition of magnesium (65.6 g, 2.7 mol), entire system was flame dried. Then, 100 mL of dry THF and 5 mL of neat 43 was added dropwise with vigorous stirring over a period of 5 minutes. When the temperature was arised to 30° C., the flask was placed in an ice bath and a solution of 43 (234 g, 1.08 mol) in THF (1 L) was added dropwise to maintain the temperature below 15° C. The mixture was stirred for 1 h at rt. The Grignard solution was titrated to 0.71 M (0.71 mol, 66%). The freshly Grignard solution was transferred in a 1 L dropping funnel. A 5 L 3-neck round bottom flask was fitted with this charged dropping funnel, an argon inlet, and a magnetic stirrer. Dry THF (0.8 L), copper chloride (3.5 g, 0.036 mol), and methyl 4-chloro-4-oxobutyrate (88 mL, 0.71 mol) were introduced into the 5 L flask and the mixture was cooled at 0° C. The Grignard solution was added dropwise over a period of 1.5 h at 0° C. After the addition, the mixture was strirred for 0.5 h at 0° C. A solution of saturated aqueous NH4Cl (1 L) was added and the mixture was extracted with ethyl acetate (3×1 L). The combined organic phase was washed with a 5% aqueous NH4OH solution (2×1 L) and brine (3×1 L), dried over magnesium sulfate, and rotary evaporated to give 121 g (65%) of crude product 44. 1H NMR (400 MHz, CDCl3) δ 1.91 (quintuplet, J=7.1 Hz, 2H), 2.56-2.66 (m, 4H), 2.76 (t, J=6.5 Hz, 2H), 3.42 (s, 3H), 3.57 (m, 4H), 3.70 (m, 5H), 4.71 (s, 2H) ppm. A 5 L 3-neck round bottom flask was fitted with a thermocouple probe was flame dried Then, 100 mL of dry THF and 5 mL of neat 43 was added dropwise was arised to 30° C. the flask was placed in an ice bath to maintain the temperature below 15° C The mixture was stirred for 1 h at rt A 5 L 3-neck round bottom flask was fitted with this charged The Grignard solution was added dropwise over a period of 1.5 h at 0° C After the addition the mixture was strirred for 0.5 h at 0° C the mixture was extracted with ethyl acetate (3×1 L) The combined organic phase was washed with a 5% aqueous NH4OH solution (2×1 L) and brine (3×1 L) dried over magnesium sulfate rotary evaporated