Sodium sulfate decahydrate → HCID 58047451, compound

HRID 1888766Notes

Reaction equation

HRID 1888766 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([C:12](OCC3CC3)=[O:13])=[C:8]([CH3:19])[CH:7]=2)[CH2:3][CH2:2]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1COCC1>[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([CH2:12][OH:13])=[C:8]([CH3:19])[CH:7]=2)[CH2:2][CH2:3]1

Participants

5

Reactant 3

HCID 62649Sodium sulfate decahydrateHCID 21226445Aluminium lithium hydrideHCID 67015834HCID 67015834, compound

Product 1

HCID 58047451HCID 58047451, compoundYield 85.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of cyclopropylmethyl 6-fluoro-4-methylpyridine-3-carboxylate (3.85 g, 18.4 mmol) obtained in Reference Example 319 and cyclopropylmethanol (1.75 mL, 22.1 mmol) in DMF (30 mL) was added 60% sodium hydride (883 mg, 22.1 mmol) under ice-cooling. After stirring for 30 min, the mixture was stirred at room temperature for 10 min. The reaction was quenched with ice, and the mixture was extracted with ethyl acetate, washed with 10% aqueous potassium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure to give cyclopropylmethyl 6-(cyclopropylmethoxy)-4-methylpyridine-3-carboxylate (4.54 g, 94%) as an oil. To a solution of the obtained cyclopropylmethyl 6-(cyclopropylmethoxy)-4-methylpyridine-3-carboxylate (4.54 g, 17.4 mmol) in THF (100 mL) was added lithium aluminum hydride (989 mg, 26.1 mmol) under ice-cooling, and the mixture was stirred for 30 min. To the reaction mixture was slowly added sodium sulfate decahydrate, and the mixture was filtered through celite. The filtrate was concentrated, the residue was dissolved in ethyl acetate, and the solution was applied to basic silica gel column chromatography (ethyl acetate). The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1) to give the title compound (2.87 g, yield 85%).

Workup

  1. temperaturecooling
  2. filtrationthe mixture was filtered through celite
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was dissolved in ethyl acetate
  5. customThe solvent was evaporated under reduced pressure
  6. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1)

Sources & evidence

ORD record
ord-acba9c35ae684bd6813f7e26818fad5c
Source dataset
uspto-grants-2013_08
Patent number
US08501804B2

Reaction notes

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