Imidazole → 8-Iodo-1,4-dioxaspiro[4.5]decane

HRID 2207794Notes

Reaction equation

HRID 2207794 reaction equation
N1C=CN=C1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[O:25]1[C:29]2([CH2:34][CH2:33][CH:32](O)[CH2:31][CH2:30]2)[O:28][CH2:27][CH2:26]1.[I:36]I>C1COCC1>[I:36][CH:32]1[CH2:33][CH2:34][C:29]2([O:28][CH2:27][CH2:26][O:25]2)[CH2:30][CH2:31]1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 5673521,4-Dioxaspiro(4.5)decan-8-ol

Product 1

HCID 110218798-Iodo-1,4-dioxaspiro[4.5]decaneYield 93.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A mixture of imidazole (111 g, 1.63 mol, 1.2 eq.), PPh3 (428 g, 1.63 mol, 1.2 eq.) and 1,4-dioxaspiro[4.5]decan-8-ol (215 g, 1.36 mol, 1.0 eq.) in THF (1.5 L) was cooled using an ice bath under N2. To this reaction mixture was added slowly a solution of I2 (414 g, 1.63 mol, 1.2 eq.) in THF (1 L) keeping the internal temperature <12° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was partitioned between H2O (2 L), EtOAc (3 L), and brine (2 L). The aqueous layer was extracted with EtOAc (1 L×2). The combined organic layer was washed with 10% aqueous NaHSO3 (800 mL, organic layer turned light yellow), brine (1 L), dried over Na2SO4, filtered, and evaporated. The crude product was dissolved in diethyl ether (6 L), filtered, and the solid was washed with diethyl ether (300 mL×3). The filtrate was concentrated and purified by column chromatography (100% hexanes to 5% EtOAc in hexanes, Rf=0.3 in 5% EtOAc in hexanes) to give 340 g (93.4% yield) of 8-iodo-1,4-dioxaspiro[4.5]decane. GC-MS: 269 (M+1).

Workup

  1. temperaturewas cooled
  2. customthe internal temperature <12° C
  3. additionAfter the addition
  4. customThe reaction mixture was partitioned between H2O (2 L), EtOAc (3 L), and brine (2 L)
  5. extractionThe aqueous layer was extracted with EtOAc (1 L×2)
  6. washThe combined organic layer was washed with 10% aqueous NaHSO3 (800 mL, organic layer turned light yellow), brine (1 L)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. dissolutionThe crude product was dissolved in diethyl ether (6 L)
  11. filtrationfiltered
  12. washthe solid was washed with diethyl ether (300 mL×3)
  13. concentrationThe filtrate was concentrated
  14. custompurified by column chromatography (100% hexanes to 5% EtOAc in hexanes, Rf=0.3 in 5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-3f9c9b6dd55543648406f2e0e4e10c14
Source dataset
uspto-grants-2016_06
Patent number
US09376450B2

Reaction notes

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