Reaction #2035319

Reaction equation

lithium diisopropylamide

heptane tetrahydrofuran ethylbenzene

1,4-dioxa-spiro[4.5]decane-8-carbonitrile

4-iodotetrahydro-2H-pyran

→

8-(tetrahydropyran-4-yl)-1,4-dioxa-spiro[4.5]decane-8-carbonitrile

8-(Tetrahydropyran-4-yl)-1,4-dioxa-spiro[4.5]decane-8-carbonitrile

Solvents

tetrahydrofuran

Conditions

Workup

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

Procedure

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+).

Source