1,4-Dioxaspiro[4.5]decan-8-one → 8-Hydroxy-8-(5-thiazolyl)-1,4-dioxaspiro[4.5]decane

HRID 2096193Notes

Reaction equation

HRID 2096193 reaction equation
C[Si](C)(C)[C:3]1[S:4][CH:5]=[CH:6][N:7]=1.[Li]CCCC.[O:15]1[C:19]2([CH2:24][CH2:23][C:22](=[O:25])[CH2:21][CH2:20]2)[O:18][CH2:17][CH2:16]1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[S:4]1[C:5]([C:22]2([OH:25])[CH2:23][CH2:24][C:19]3([O:18][CH2:17][CH2:16][O:15]3)[CH2:20][CH2:21]2)=[CH:6][N:7]=[CH:3]1

Participants

6

Reactant 4

HCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 5884532-TrimethylsilylthiazoleHCID 2724141Tetrabutylammonium FluorideHCID 178418339Butyllithium

Product 1

HCID 590174418-Hydroxy-8-(5-thiazolyl)-1,4-dioxaspiro[4.5]decane

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

A solution of 2-trimethylsilanyl-thiazole (Fluka, 5.0 g, 31.8 mmol) in THF (20 mL) at −78° C. was treated with n-BuLi (2.5 M in hexanes, 15.3 mL, 38.2 mmol) dropped slowly over 10 min. The reaction was stirred for an additional 20 min. at −78° C. A solution of 1,4-dioxa-spiro[4.5]decan-8-one (Aldrich, 6.0 g, 38 mmol) in THF (15 mL) was slowly dropped into the reaction. After addition, the reaction was stirred for an additional 2 hours at −78° C. The reaction was then quenched with water and warmed to room temperature. The solvent was removed in vacuo and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered and concentrated to give a yellow solid. To this solid in THF (20 mL) was added TBAF (1.0 N in THF, 30 mL) at room temperature. The reaction was stirred for 1 hour. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, concentrated and then purified by silica gel column on a CombiFlash® system using hexanes and ethyl acetate (from 10% ethyl acetate to 100% ethyl acetate) to afford the title compound as a white solid.

Workup

  1. additiondropped slowly over 10 min
  2. additionAfter addition
  3. stirringthe reaction was stirred for an additional 2 hours at −78° C
  4. customThe reaction was then quenched with water
  5. temperaturewarmed to room temperature
  6. customThe solvent was removed in vacuo
  7. customthe residue was partitioned between ethyl acetate and water
  8. washThe organic layer was washed with brine
  9. dry with materialdried over anhydrous Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a yellow solid
  13. stirringThe reaction was stirred for 1 hour
  14. customThe solvent was removed
  15. customthe residue was partitioned between ethyl acetate and water
  16. washThe organic layer was washed with brine
  17. dry with materialdried over anhydrous Na2SO4
  18. filtrationfiltered
  19. concentrationconcentrated
  20. custompurified by silica gel column on a CombiFlash® system

Sources & evidence

ORD record
ord-28b14e61e93346e58b2e256147cb092b
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

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