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

HRID 1948137Notes

Reaction equation

HRID 1948137 reaction equation
C([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.[O:29]1[C:33]2([CH2:38][CH2:37][CH:36]([C:39]#[N:40])[CH2:35][CH2:34]2)[O:32][CH2:31][CH2:30]1.I[CH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1>O1CCCC1>[O:45]1[CH2:46][CH2:47][CH:42]([C:36]2([C:39]#[N:40])[CH2:37][CH2:38][C:33]3([O:32][CH2:31][CH2:30][O:29]3)[CH2:34][CH2:35]2)[CH2:43][CH2:44]1

Participants

6

Reactant 4

HCID 2724682Lithium diisopropylamideHCID 27955064-iodotetrahydro-2H-pyranHCID 111164331,4-Dioxaspiro[4.5]decane-8-carbonitrileHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 670728278-(Tetrahydropyran-4-yl)-1,4-dioxa-spiro[4.5]decane-8-carbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

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+).

Workup

  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)

Sources & evidence

ORD record
ord-1df67581b358474cb6983235baa822ec
Source dataset
uspto-grants-2013_03
Patent number
US08399482B2

Reaction notes

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