Sodium hydride → 2-Butanol, 4-[(5-bromo-6-methyl-2-pyridinyl)oxy]-2-methyl-

HRID 576666Notes

Reaction equation

HRID 576666 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:5]=[CH:6][C:7]([OH:11])=[N:8][C:9]=1[CH3:10].CC1C=CC(S(O[CH2:23][CH2:24][C:25]([OH:28])([CH3:27])[CH3:26])(=O)=O)=CC=1.[Cl-].[NH4+]>CN(C)C=O>[Br:3][C:4]1[CH:5]=[CH:6][C:7]([O:11][CH2:23][CH2:24][C:25]([CH3:27])([OH:28])[CH3:26])=[N:8][C:9]=1[CH3:10]

Participants

6

Reactant 4

HCID 24758Sodium hydride2×HCID 25517Ammonium ChlorideHCID 140012952-Methyl-4-[(4-methylbenzenesulfonyl)oxy]butan-2-ol2×HCID 178433439HCID 178433439, compound

Product 1

HCID 577874102-Butanol, 4-[(5-bromo-6-methyl-2-pyridinyl)oxy]-2-methyl-Yield 89.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of sodium hydride (containing about 40% of a mineral oil, 0.38 g) in N,N-dimethylformamide (10 mL), 5-bromo-2-hydroxy-6-methylpyridine (1.00 g) and 3-hydroxy-3-methylbutyl 4-methylbenzenesulfonate (1.51 g) were added under ice-cooling and the resultant reaction mixture was stirred at 60° C. for 2.5 hours. To the mixture, 3-hydroxy-3-methylbutyl 4-methylbenzenesulfonate (0.50 g) was further added and the resultant reaction mixture was stirred at 60° C. for 1.5 hours. Sodium hydride (containing about 40% of a mineral oil, 40 mg) was further added. To the reaction mixture, a saturated aqueous ammonium chloride solution was added and the mixture was extracted with ethyl acetate. The organic phase was washed with brine and then dried over anhydrous sodium sulfate. From the organic phase, the solvent was removed by evaporation under reduced pressure and the resultant residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=50:50 to 33:67) to give the title compound (1.3 g) as a pale yellow oil.

Workup

  1. temperaturecooling
  2. customthe resultant reaction mixture
  3. customthe resultant reaction mixture
  4. stirringwas stirred at 60° C. for 1.5 hours
  5. additionwas further added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic phase was washed with brine
  8. dry with materialdried over anhydrous sodium sulfate
  9. customFrom the organic phase, the solvent was removed by evaporation under reduced pressure
  10. customthe resultant residue was purified by silica gel column chromatography (eluent; n-hexane:ethyl acetate=50:50 to 33:67)

Sources & evidence

ORD record
ord-cae822a22f4f4649915877d71f328827
Source dataset
uspto-grants-2015_05
Patent number
US09040525B2

Reaction notes

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