Hexane → 8-(5-Bromo-3-methylpyridin-2-yl)-1,4-dioxaspiro[4,5]decan-8-ol

HRID 1748525Notes

Reaction equation

HRID 1748525 reaction equation
CCCCCC.C([Li])CCC.Br[C:13]1[C:18]([CH3:19])=[CH:17][C:16]([Br:20])=[CH:15][N:14]=1.[CH2:21]1[O:31][C:24]2([CH2:29][CH2:28][C:27](=[O:30])[CH2:26][CH2:25]2)[O:23][CH2:22]1>C1(C)C=CC=CC=1.O>[Br:20][C:16]1[CH:17]=[C:18]([CH3:19])[C:13]([C:27]2([OH:30])[CH2:28][CH2:29][C:24]3([O:31][CH2:21][CH2:22][O:23]3)[CH2:25][CH2:26]2)=[N:14][CH:15]=1

Participants

7

Reactant 4

HCID 8058HexaneHCID 5674151,4-Dioxaspiro[4.5]decan-8-oneHCID 8176802,5-Dibromo-3-methylpyridineHCID 178418339Butyllithium

Product 1

HCID 866924748-(5-Bromo-3-methylpyridin-2-yl)-1,4-dioxaspiro[4,5]decan-8-olYield 55.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

1.6M n-Hexane solution of n-butyl lithium (100 ml) was added dropwise under nitrogen atmosphere at −78° C. to a solution of 2,5-dibromo-3-picoline (38.3 g) in toluene (300 ml), and stirred at the same temperature for two hours. Then, a solution of 1,4-cyclohexanedione monoethyleneketal (25 g) in toluene (200 ml) was added slowly dropwise, and after the addition the mixture was stirred at the same temperature for an hour. Then, the reaction solution was warmed up slowly to room temperature under stirring. After completion of the reaction, water was added and extracted with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous sodium sulfate and concentrated. Acetonitrile and water were added to the residue and the precipitate was filtered and dried at 60° C. under air blow to give 8-(5-bromo-3-methylpyridin-2-yl)-1,4-dioxaspiro[4,5]decan-8-ol (28 g) as a light brown solid.

Workup

  1. additionafter the addition the mixture
  2. stirringwas stirred at the same temperature for an hour
  3. stirringunder stirring
  4. additionwas added
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with water and saturated brine successively
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. additionAcetonitrile and water were added to the residue
  10. filtrationthe precipitate was filtered
  11. customdried at 60° C. under air blow

Sources & evidence

ORD record
ord-5d9205395f55462b94f4c1b1eb9877e6
Source dataset
uspto-grants-2015_10
Patent number
US09150555B2

Reaction notes

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