反应详情

温度

12.5 °C

A 3-neck 1-L round bottom flask was equipped with a thermometer, dropping funnel and nitrogen inlet. Under an atmosphere of N2, a solution of 1M lithium aluminum hydride in THF (900 mL, 900 mmol) was added and cooled using a dry ice/acetone bath. To this was added drop-wise a solution of diethyl 1,4-dioxaspiro[4.5]decane-8,8-dicarboxylate, Intermediate 3, (128.7 g, 450 mmol) in THF (75 mL) over a period of 1 h while maintaining the internal temperature at 10-15° C. The mixture was left in the cooling bath and allowed to regain room temperature while stirring overnight. The mixture was then cooled to −5° C. and quenched by the slow addition of water (40 mL) under vigorous stirring over 1.5 hours being careful to maintain the internal temperature below 30° C. To this was added drop-wise 15% NaOH (40 mL) and water (40 mL). The resulting precipitate was filtered over Celite, and washed with THF (300 mL). The filtrate was concentrated in vacuo to dryness to provide the title compound (63.3 g) as a white solid. Further extraction of the white cake with 10% MeOH/CH2Cl2 (2×500 mL) gave an additional amount (15.6 g) of the title compound. This constitutes total combined yield of 78.9 g (0.39 mol, Y. 87%). LCMS: m/z 203 (M+H), 225 (M+Na). 1HNMR (500 MHz, CD3OD) δ ppm 1.49-1.55 (4H, m, 3,5-CH2), 1.59-1.66 (4H, m, 2,6-CH2), 3.49 (4H, s, 9,10-OCH2), 3.94 (4H, s, 7,8-OCH2). 13C NMR (126 MHz, CD3OD) δ ppm 26.7 (3,5-CH2), 30.3 (2,6-CH2), 38.3 (4-C), 64.2 (7,8-OCH2), 65.4 (9,10-OCH2), 109.2 (1-OCO).

1. customA 3-neck 1-L round bottom flask was equipped with a thermometer
2. temperaturecooled
3. waitThe mixture was left in the cooling bath
4. customto regain room temperature
5. temperatureThe mixture was then cooled to −5° C.
6. customquenched by the slow addition of water (40 mL)
7. stirringunder vigorous stirring over 1.5 hours
8. temperatureto maintain the internal temperature below 30° C
9. additionTo this was added drop-wise 15% NaOH (40 mL) and water (40 mL)
10. filtrationThe resulting precipitate was filtered over Celite
11. washwashed with THF (300 mL)
12. concentrationThe filtrate was concentrated in vacuo to dryness