반응 #2035319

ord-1df67581b358474cb6983235baa822ec

반응 조건

온도
-78°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

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

실험 절차

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+).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08399482B2uspto-grants-2013_03