2-Bromopropane → (2-Isopropoxypyridin-3-yl)methanol

HRID 384101Notes

Reaction equation

HRID 384101 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(=O)([O-])[O-].[K+].[K+].[Cl-].[NH4+].[H-].[Al+3].[Li+].[H-].[H-].[H-].O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+].Br[CH:44]([CH3:46])[CH3:45]>CN(C)C=O.O1CCCC1>[CH:44]([O:1][C:2]1[C:3]([CH2:4][OH:6])=[CH:8][CH:9]=[CH:10][N:11]=1)([CH3:46])[CH3:45]

Participants

9

Reactant 6

HCID 63582-BromopropaneHCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 62649Sodium sulfate decahydrateHCID 21226445Aluminium lithium hydrideHCID 178498115HCID 178498115, compound

Product 1

HCID 45480195(2-Isopropoxypyridin-3-yl)methanol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of methyl 2-hydroxynicotinate (250 mg) in dimethylformamide (3 ml), 0.459 ml of 2-bromopropane and 676 mg of potassium carbonate were added, and the reaction solution was stirred at 50° C. for 5 hours and at 70° C. for 3 hours. The reaction solution was cooled, then a saturated aqueous ammonium chloride solution was added, and the mixture was 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 colorless oil. To a solution of lithium aluminum hydride (247 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 for 2 hours under ice-cooling, 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 (98:2-50:50)) to afford the title compound as a colorless oil.

Workup

  1. temperatureThe reaction solution was cooled
  2. extractionthe mixture was extracted 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 colorless oil
  7. temperaturecooling
  8. stirringThe reaction solution was stirred for 2 hours under ice-
  9. temperaturecooling
  10. stirringfurther stirring the mixture at the same temperature for 1 hour
  11. filtrationThe reaction solution was Celite-filtered
  12. distillationthe filtrate was distilled off under reduced pressure
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50))

Sources & evidence

ORD record
ord-9908f50ce63d4e40878130a7aba5c76e
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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