1256546-71-0

1256546-72-1

The synthesis of 1,4-dioxaspiro[4.5]decane-8,8-dicarboxylic acid diethyl ester (Intermediate 3, 128.7 g, 450 mmol) was carried out as a raw material for the synthesis of 1,4-dioxaspiro[4.5]decane-8,8-dimethanol (Intermediate 4). The procedure was as follows: a THF solution (900 mL, 900 mmol) of 1 M lithium aluminum hydride was added to a 3-necked 1 L round-bottomed flask equipped with a thermometer, a dropping funnel, and a nitrogen inlet under nitrogen protection and cooled using a dry ice/acetone bath until the internal temperature was maintained at 10-15 °C. The THF solution (75 mL) of intermediate 3 was added slowly and dropwise over a period of 1 hr. The reaction mixture was gradually brought back to room temperature in a cooling bath and stirred overnight. Subsequently, the mixture was cooled to -5°C and quenched by the slow addition of water (40 mL) under vigorous stirring for 1.5 h. The reaction was carried out during 1.5 h, during which the internal temperature was strictly controlled not to exceed 30°C. Next, 15% NaOH solution (40 mL) and water (40 mL) were added dropwise. The precipitate obtained was filtered through diatomaceous earth and washed with THF (300 mL). The filtrate was concentrated to dryness in vacuum to afford 1,4-dioxaspiro[4.5]decane-8,8-dimethanol (63.3 g) as a white solid. The white filter cake was further extracted with 10% MeOH/CH2Cl2 (2 x 500 mL) to obtain additional product (15.6 g). The total yield was 78.9 g (0.39 mol, 87% yield). The product was characterized by LCMS and NMR: LCMS m/z 203 (M+H), 225 (M+Na); 1H NMR (500MHz, 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 (126MHz, 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).