Thiazole → 8-(1,3-Thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol

HRID 1039936Notes

Reaction equation

HRID 1039936 reaction equation
[S:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[O:11]1[C:15]2([CH2:20][CH2:19][C:18](=[O:21])[CH2:17][CH2:16]2)[O:14][CH2:13][CH2:12]1>C1COCC1>[S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[C:18]1([OH:21])[CH2:19][CH2:20][C:15]2([O:14][CH2:13][CH2:12][O:11]2)[CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 178418339Butyllithium

Product 1

HCID 578033298-(1,3-Thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-olYield 85.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-10 °C

Procedure

Thiazole (25.0 mL, 352 mmol) was diluted with THF (300 mL) and cooled to −780° C. n-BuLi (220 mL, 352 mmol) was added at such a rate that the internal temperature did not exceed −65 C. A yellow slurry formed and the addition took 40 min. The reaction was aged for 20 min then 1,4-dioxaspiro[4.5]decan-8-one (50 g, 320 mmol) was added as a solution in THF (420 mL) dropwise via addition funnel. After 2 h, the reaction was quenched with water, the cooling bath removed and the mixture stirred until the internal temperature reached 0° C. The mixture was diluted with EtOAc and the layers were separated followed by extraction of the aqueous portion with EtOAc. The combined organics were dried with MgSO4, filtered, and concentrated to a viscous orange oil. EtOAc was added and concentrated to 100 mL. Hexanes was added dropwise via an addition funnel. The mixture was stirred for 1 h then cooled to −10° C. and filtered. The white cake was washed with hexanes (2×) then dried under a nitrogen bag to afford 8-(1,3-thiazol-2-yl)-1,4-dioxaspiro[4.5]decan-8-ol (66 g, 85%) as a white solid.

Workup

  1. additionwas added at such a rate that the internal temperature
  2. customA yellow slurry formed
  3. additionthe addition
  4. waitThe reaction was aged for 20 min
  5. waitAfter 2 h
  6. customthe reaction was quenched with water
  7. customthe cooling bath removed
  8. customreached 0° C
  9. additionThe mixture was diluted with EtOAc
  10. customthe layers were separated
  11. extractionfollowed by extraction of the aqueous portion with EtOAc
  12. dry with materialThe combined organics were dried with MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated to a viscous orange oil
  15. additionEtOAc was added
  16. concentrationconcentrated to 100 mL
  17. additionHexanes was added dropwise via an addition funnel
  18. stirringThe mixture was stirred for 1 h
  19. filtrationfiltered
  20. washThe white cake was washed with hexanes (2×)
  21. customthen dried under a nitrogen bag

Sources & evidence

ORD record
ord-e8ebd510b2cb4552a92b0c0ca353c2a3
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

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