Isobutylene oxide → 5-Bromo-1-(2-hydroxy-2-methylpropyl)-2(1H)-pyridinone

HRID 877433Notes

Reaction equation

HRID 877433 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH3:9][C:10]1([CH3:13])[CH2:12][O:11]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:9][C:10]([OH:11])([CH3:13])[CH3:12])[CH:7]=1

Participants

6

Reactant 3

HCID 11208Isobutylene oxideHCID 11430Potassium CarbonateHCID 5995285-Bromo-2-hydroxypyridine

Product 1

HCID 596357485-Bromo-1-(2-hydroxy-2-methylpropyl)-2(1H)-pyridinoneYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromopyridin-2(1H)-one (600 mg, 3.5 mmol), 2,2-dimethyloxirane (750 mg, 10 mmol) and K2CO3 (960 mg, 6.9 mmol) in DMF (3 mL) was heated at 100° C. for 2 hours. The reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with ethyl acetate (80 mL), washed with water, brine, and dried over MgSO4. The organic layer was filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (eluting with 10 to 50% EtOAc/hexane) to give Compound B387a (650 mg, 76% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.50 (d, J=2.6 Hz, 1H), 7.40 (dd, J=9.6, 2.8 Hz, 1H), 6.54 (d, J=9.7 Hz, 1H), 3.99 (s, 2H), 3.57-3.39 (s, 1H), 1.27 (s, 6H).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with water, brine
  3. dry with materialdried over MgSO4
  4. filtrationThe organic layer was filtered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (eluting with 10 to 50% EtOAc/hexane)
  7. customto give Compound B387a (650 mg, 76% yield)

Sources & evidence

ORD record
ord-7c2c0f79c9e641af8ce09341d2f9188e
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

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