1,4-Dioxaspiro[4.5]decan-8-one → 8-Hydroxy-8-(6-methoxy-3-pyridyl)-1,4-dioxaspiro[4.5]decane

HRID 2388295Notes

Reaction equation

HRID 2388295 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([O:8][CH3:9])=[N:6][CH: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>C1COCC1.CCOCC>[CH3:9][O:8][C:5]1[N:6]=[CH:7][C:2]([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:3][CH:4]=1

Participants

6

Reactant 3

HCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 27348955-Bromo-2-methoxypyridineHCID 178418339Butyllithium

Product 1

HCID 595560668-Hydroxy-8-(6-methoxy-3-pyridyl)-1,4-dioxaspiro[4.5]decane

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-methoxy-pyridine (Aldrich, 5.0 g, 26.6 mmol) in THF or ether (30 mL) at −78° C. was treated with n-BuLi (2.5 M in hexanes, 12 mL, 30 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, 4.37 g, 28 mmol) in THF (10 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, which was then purified by silica gel column on a CombiFlash® system (Teledyne Isco, Inc, Lincoln, Nebr.) using hexanes and ethyl acetate (from 10% ethyl acetate to 100% ethyl acetate) to afford the title compound as a yellow 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, which
  13. customwas then purified by silica gel column on a CombiFlash® system (Teledyne Isco, Inc, Lincoln, Nebr.)

Sources & evidence

ORD record
ord-b4ecb3543657441885d66f86b47b913d
Source dataset
uspto-grants-2012_09
Patent number
US08269015B2

Reaction notes

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