Tetrahydrofuran → (2-(Cyclopentyloxy)pyridin-3-yl)methanol

HRID 384099Notes

Reaction equation

HRID 384099 reaction equation
[OH:1][C:2]1[N:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=O.[C:12](=O)([O-])[O-].[K+].[K+].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].O1[CH2:45][CH2:44][CH2:43][CH2:42]1>CN(C)C=O.BrC1CC1.[Cl-].[NH4+]>[CH:42]1([O:1][C:2]2[C:3]([CH2:4][OH:6])=[CH:8][CH:9]=[CH:10][N:11]=2)[CH2:12][CH2:45][CH2:44][CH2:43]1

Participants

9

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 11430Potassium CarbonateHCID 62649Sodium sulfate decahydrateHCID 21226445Aluminium lithium hydrideHCID 178498115HCID 178498115, compound

Product 1

HCID 61258189(2-(Cyclopentyloxy)pyridin-3-yl)methanol

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolventHCID 78037BromocyclopropaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of methyl 2-hydroxynicotinate (300 mg) in dimethylformamide (3 ml), 0.42 ml of bromocyclopropane and 542 mg of potassium carbonate were added, and the reaction solution was stirred overnight at 50° C. The reaction solution was cooled, then diluted with a saturated aqueous ammonium chloride solution, and extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a yellow oil. To a solution of lithium aluminum hydride (143 mg) in tetrahydrofuran (2 ml), a solution of the crude product in tetrahydrofuran 3 ml was added under ice-cooling. The reaction solution was stirred at the same temperature for 1 hour, followed by adding sodium sulfate decahydrate and further stirring the mixture at the same temperature for 1 hour. The reaction solution was Celite-filtered, the filtrate was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (95:5-50:50)) to afford the title compound as a colorless oil.

Workup

  1. temperatureThe reaction solution was cooled
  2. extractionextracted with ethyl acetate
  3. washThe combined organic layers were washed with a saturated saline solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customto afford a crude product as a yellow oil
  7. temperaturecooling
  8. stirringThe reaction solution was stirred at the same temperature for 1 hour
  9. stirringfurther stirring the mixture at the same temperature for 1 hour
  10. filtrationThe reaction solution was Celite-filtered
  11. distillationthe filtrate was distilled off under reduced pressure
  12. customthe residue obtained
  13. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (95:5-50:50))

Sources & evidence

ORD record
ord-f265eaa0dad7484a91cc96619eec371c
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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