反应详情

温度

-78 °C

To a 2M solution of lithium diisopropylamide in heptane/tetrahydrofuran/ethylbenzene (18 mL, 35.9 mmol, 1.5 eq.) at −78° C. was added dropwise a solution of 1,4-dioxa-spiro[4.5]decane-8-carbonitrile (commercially available or via literature procedure described for example in Becker et al. Synthesis 1992, 11, 1080-1082; 4.0 g, 23.9 mmol) in tetrahydrofuran (40 mL). After stirring for 30 min at −78° C., 4-iodotetrahydro-2H-pyran (5.1 g, 23.9 mmol, 1 eq.) was added carefully. The reaction mixture was allowed to warm to room temperature over night before being quenched by slow addition of ethanol (10 mL) and water (20 mL) subsequently. The resulting suspension was filtered through celite and extracted three times with dichloromethane. The combined organic phases were concentrated in vacuo and purified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane) to give 2.80 g of 8-(tetrahydropyran-4-yl)-1,4-dioxa-spiro[4.5]decane-8-carbonitrile (5). Rt=1.03 min (Method B). Detected mass: 252.3 (M+H+).

1. temperatureto warm to room temperature over night
2. custombefore being quenched by slow addition of ethanol (10 mL) and water (20 mL) subsequently
3. filtrationThe resulting suspension was filtered through celite
4. extractionextracted three times with dichloromethane
5. concentrationThe combined organic phases were concentrated in vacuo
6. custompurified by flash chromatography (SiO2, 0%→30% methanol in dichloromethane)