Imidazole → 3-tert-Butyldimethylsilyloxy-1H-pyridin-2-one

HRID 42274Notes

Reaction equation

HRID 42274 reaction equation
[OH:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][CH:7]=1.N1C=CN=C1.[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].O>CN(C)C=O>[Si:14]([O:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][CH:7]=1)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 281152,3-DihydroxypyridineHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 116371753-tert-Butyldimethylsilyloxy-1H-pyridin-2-oneYield 53.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

3-Hydroxypyridin-2(1H)-one (15 g, 135 mmol) and imidazole (23 g, 338 mmol) were suspended in dimethylformamide (200 mL) under inert atmosphere. A solution of tert-butyldimethylsilyl chloride (20.5 g, 136 mmol) in dimethylformamide (200 mL) is added dropwise at room temperature over 30 minutes. The reaction was then allowed to stir overnight. The resulting solution was then poured into water (300 mL) and the mixture extracted with tert-butyl methyl ether (3×500 mL). The combined organic layer was washed with water (300 mL), brine (300 mL) then dried over Na2SO4. The solvent is removed under reduced pressure and the crude product crystallized from heptanes to afford 16.3 g (53% yield) of the desired product. 1H NMR (250 MHz, CDCl3) δ ppm 12.98 (1H, m); 6.91 (1H, dd, J=1. Hz, J=6.8 Hz); 6.81 (1H, dd, J=1.8 Hz, J=7.2 Hz); 6.02-6.007 (1H, m); 0.90 (9H, s), and 0.17 (6H, s).

Workup

  1. extractionthe mixture extracted with tert-butyl methyl ether (3×500 mL)
  2. washThe combined organic layer was washed with water (300 mL), brine (300 mL)
  3. dry with materialthen dried over Na2SO4
  4. customThe solvent is removed under reduced pressure
  5. customthe crude product crystallized from heptanes

Sources & evidence

ORD record
ord-e79b1151b6ee47e7a1deda62b9b5b6e5
Source dataset
uspto-grants-2013_09
Patent number
US08536181B2

Reaction notes

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