Sodium hydride → 1-(2-(Benzyloxy)ethyl)-5-bromopyridin-2(1H)-one

HRID 1878727Notes

Reaction equation

HRID 1878727 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[H-].[Na+].Br[CH2:12][CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[NH4+].[Cl-]>CN(C=O)C>[CH2:15]([O:14][CH2:13][CH2:12][N:6]1[CH:7]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]1=[O:8])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 73833Benzene, ((2-bromoethoxy)methyl)-HCID 5995285-Bromo-2-hydroxypyridine

Product 1

HCID 598430091-(2-(Benzyloxy)ethyl)-5-bromopyridin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a stirring solution of 5-bromo-2(1 h)-pyridone (2000 mg, 11.5 mmol) in DMF (15 mL) at 0° C. was added NaH (60% dispersion in mineral oil, 552 mg, 23.0 mmol). After 1 h then 1-((2-bromoethoxy)methyl)benzene (2.00 mL, 12.6 mmol) was added. The reaction mixture was heated to 50° C. for 18 h. NH4Cl (satd.) was added and the mixture was partitioned between EtOAc and water. The aqueous layer was extracted twice with EtOAc (50 mL) and the combined organic was washed with satd. NH4Cl and dried over MgSO4. The organic was concentrated to an oil by repeatedly azeotroping with toluene. This residue was purified on 40 grams of silica eluting with 15-30% of EtOAc/hexanes to give a colorless oil that crystallized upon sitting for 2 weeks. MS (ESI pos. ion) m/z (MH+): 308/310. Calc'd exact mass for C14H14BrNO2: 307. 1H NMR (400 MHz, Chloroform-d) δ ppm 3.71-3.76 (m, 2 H) 4.08-4.13 (m, 2 H) 4.48 (s, 2 H) 6.46 (d, J=9.78 Hz, 1H) 7.21-7.38 (m, 6 H) 7.54 (d, J=2.74 Hz, 1 H).

Workup

  1. customthe mixture was partitioned between EtOAc and water
  2. extractionThe aqueous layer was extracted twice with EtOAc (50 mL)
  3. washthe combined organic was washed with satd
  4. dry with materialNH4Cl and dried over MgSO4
  5. concentrationThe organic was concentrated to an oil
  6. customby repeatedly azeotroping with toluene
  7. customThis residue was purified on 40 grams of silica eluting with 15-30% of EtOAc/hexanes
  8. customto give a colorless oil that
  9. customcrystallized
  10. waitupon sitting for 2 weeks

Sources & evidence

ORD record
ord-a978aeff44c84ce39ef8844168d298ce
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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