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

HRID 1190852Notes

Reaction equation

HRID 1190852 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, 10.4 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 244a (650 mg, 76% yield). 1H NMR (400 MHz, CDCl3) 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)

Sources & evidence

ORD record
ord-641891c684054ed89ae5d936144c7f6c
Source dataset
uspto-grants-2014_03
Patent number
US08680090B2

Reaction notes

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