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

HRID 2096185Notes

Reaction equation

HRID 2096185 reaction equation
[Li]CCCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[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:6]1[CH:10]=[CH:9][N:8]=[C:7]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-ol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-BuLi (2.5 M in hexanes, 26 mL, 65 mmol) was dropped slowly into a solution of thiazole (Aldrich, 5.0 g, 59 mmol) in THF (50 mL) at −78° C. over 10 min. The reaction was stirred for additional 20 min. at −78° C. A solution of 1,4-dioxa-spiro[4.5]decan-8-one (9.36 g, 60 mmol) in THF (20 mL) was slowly dropped into the reaction. After addition, the reaction was stirred for additional 2 hours at −78° C. The reaction was then quenched with water solution 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 yellow solid, which was 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. additionAfter addition
  2. stirringthe reaction was stirred for additional 2 hours at −78° C
  3. customThe reaction was then quenched with water solution
  4. temperaturewarmed to room temperature
  5. customThe solvent was removed in vacuo
  6. customthe residue was partitioned between ethyl acetate and water
  7. washThe organic layer was washed with brine
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give yellow solid, which
  12. customwas then purified by silica gel column on a CombiFlash® system

Sources & evidence

ORD record
ord-61a15c6f56b6438883190f8153484b37
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

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