Sodium hydride → 2-Methyl-8-hydroxyquinoline

HRID 889222Notes

Reaction equation

HRID 889222 reaction equation
FC1C=CC=CC=1CO.[H-].[Na+].Cl[C:13]1[C:22]2[C:17](=[C:18]([OH:23])[CH:19]=[CH:20][CH:21]=2)[N:16]=[C:15]([CH3:24])[CH:14]=1>CN(C=O)C>[CH3:24][C:15]1[CH:14]=[CH:13][C:22]2[C:17](=[C:18]([OH:23])[CH:19]=[CH:20][CH:21]=2)[N:16]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 679692-Fluorobenzylic alcoholHCID 122197224-Chloro-8-hydroxy-2-methylquinoline

Product 1

HCID 132242-Methyl-8-hydroxyquinoline

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
130 °C

Procedure

To a stirred solution of 2-fluorobenzyl alcohol (1.95 g, 15.5 mmol) in anhydrous DMF (35 mL) was added sodium hydride (60% in mineral oil, 0.62 g, 15.5 mmol). After 30 min the 4-chloro-2-methylquinolin-8-ol (1.00 g, 5.16 mmol) was added and resulting mixture was heated at 130° C. for 20 h under nitrogen atmosphere. The mixture was cooled, poured into ice/NaHCO3 and extracted with EtOAc. Evaporation gave a crude oil that was purified by silica chromatography eluting with a gradient of 1% to 10% of MeOH/DCM to give 44(2-fluorobenzyl)oxy)-2-methylquinolin-8-ol as an oil that solidified on standing (0.39 g, 27%). LCMS (+APCI) 284 (M+1), mp 124-125° C. 1H-NMR (CDCl3, δ): 7.75 (d, J=8.4 Hz, 1H), 7.50 (d, J=7.6 Hz, 2H), 7.43 (s, 1H), 7.35 (m, 3H), 7.20 (d, J=7.6 Hz, 1H), 7.06 (d, J=8.0 Hz), 5.45 (s, 2H), 2.78 (s, 3H).

Workup

  1. customresulting mixture
  2. temperatureThe mixture was cooled
  3. extractionextracted with EtOAc
  4. customEvaporation
  5. customgave a crude oil that
  6. customwas purified by silica chromatography
  7. washeluting with a gradient of 1% to 10% of MeOH/DCM

Sources & evidence

ORD record
ord-18ee85ea6c0244339ff1e09b3153d20c
Source dataset
uspto-grants-2012_08
Patent number
US08252793B2

Reaction notes

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