Sodium hydride → (R)-5-(Oxiran-2-ylmethoxy)quinoline

HRID 393975Notes

Reaction equation

HRID 393975 reaction equation
[H-].[Na+].[OH:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2.S(C1C=CC(C)=CC=1)(O[CH2:18][C@@H:19]1[O:21][CH2:20]1)(=O)=O>CN(C=O)C>[O:21]1[CH2:20][C@@H:19]1[CH2:18][O:3][C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[CH:7][CH:8]=[N:9]2

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 154187Glycidyl tosylate, (R)-HCID 135441757Quinolin-5-ol

Product 1

HCID 11735808(R)-5-(Oxiran-2-ylmethoxy)quinolineYield 71.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Conditions

Temperature
5 °C

Procedure

Sodium hydride (60 weight %; 1.79 g; 44.8 mmol) is washed with hexanes (3×10 mL) under an argon blanket. DMF (17 mL) is then added at ambient temperature and the stirred slurry is cooled to 5° C. A solution of 5-hydroxyquinoline (5.00 g; 34.4 mmol) in DMF (65 mL) is added dropwise over 30 minutes. The resulting mixture is allowed to warm to ambient temperature over 1 hour affording a clear, reddish-brown solution. A solution of (R)-(−)-glycidyl tosylate (10.22 g; 44.8 mmol) in DMF (50 mL) is added dropwise over 20 minutes. The resulting mixture is stirred at ambient temperature for 4 hours, quenched by the addition of saturated aqueous ammonium chloride (25 mL), poured onto water (750 mL), and extracted with ether (3×375 mL). The combined ether layers are washed with saturated aqueous sodium bicarbonate (2×375 mL), then dried over MgSO4, filtered, and concentrated in vacuo. The residue is purified via silica gel chromatography with gradient elution (33%→50% ethyl acetate in hexanes) affording the desired product (4.95 g) as a tan solid. ESMS: MH+ 202.2 (base).

Workup

  1. temperatureto warm to ambient temperature over 1 hour
  2. customaffording a clear, reddish-brown solution
  3. customquenched by the addition of saturated aqueous ammonium chloride (25 mL)
  4. additionpoured onto water (750 mL)
  5. extractionextracted with ether (3×375 mL)
  6. washThe combined ether layers are washed with saturated aqueous sodium bicarbonate (2×375 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue is purified via silica gel chromatography with gradient elution (33%→50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-6620af1544c0461a92ae36620da9a15d
Source dataset
uspto-grants-2004_10
Patent number
US06809093B2

Reaction notes

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