Potassium Iodide → 1-(4-chlorobenzyl)-3-hydroxypyridin-2(1H)-one

HRID 1050916Notes

Reaction equation

HRID 1050916 reaction equation
[OH:1][C:2]1[C:3](=[O:8])[NH:4][CH:5]=[CH:6][CH:7]=1.C[Si](C)(C)N[Si](C)(C)C.[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][CH:20]=1.[I-].[K+]>C(#N)C.S([O-])([O-])(=O)=O.[NH4+].[NH4+].O>[Cl:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23][N:4]2[CH:5]=[CH:6][CH:7]=[C:2]([OH:1])[C:3]2=[O:8])=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 4875Potassium IodideHCID 77231-Chloro-4-(chloromethyl)benzeneHCID 13838HexamethyldisilazaneHCID 281152,3-Dihydroxypyridine

Product 1

HCID 529122191-(4-chlorobenzyl)-3-hydroxypyridin-2(1H)-oneYield 86.2%

Reagents, catalysts & solvents 3

HCID 6097028Ammonium SulfateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent2×

Procedure

to a nitrogen purged 1-L round bottom flask equipped with a mechanical stirrer, upright condenser, and thermometer was charged 3-hydroxypyridin-2(1H)-one [2,3-dihydroxypyridine] (40.0 g, 0.36 mol, 1 equiv.) [CAS No. 16867-04-2], ammonium sulfate (2.4 g, 0.02 mol, 0.05 equiv.) and acetonitrile (200 mL, 5 parts v/w). The resulting suspension was stirred at room temperature. Hexamethyldisilazane (116.2 g, 0.72 mol, 2 equiv.) is added dropwise. The resulting suspension was heated to reflux for 4 hours. The solution was then cooled to room temperature followed by the addition of a solution of 4-chlorobenzyl chloride (63.8 g, 0.4 mol, 1.1 equiv.) in acetonitrile (40 mL, 1 part v/w). Potassium iodide (59.8 g, 0.36 mol, 1 equiv.) is then added. The solution was then brought to reflux for 16 hours. The solution was cooled to 5° C. and water (240 mL) was slowly added over 15 minutes. The reaction mixture was allowed to warm to room temperature and stirring was continued for 2 hours. The solution was filtered under vacuum and rinsed with water (360 mL). The filter cake is then washed with methyl tert-butyl ether (360 mL). The resulting green-brown solid is vacuum dried to afford 63.5 g (86.2%) of the desired product. 1H NMR (DMSO-d6) δ ppm 7.4 (d, 2H), 7.3 (d, 1H), 7.2 (d, 2H), 6.7 (d, 1H), 6.1 (t, 1H), and 5.1 (s, 2H).

Workup

  1. customto a nitrogen purged 1-L round bottom flask
  2. customequipped with a mechanical stirrer
  3. temperatureThe resulting suspension was heated
  4. temperatureto reflux for 4 hours
  5. temperatureThe solution was then cooled to room temperature
  6. temperatureto reflux for 16 hours
  7. temperatureThe solution was cooled to 5° C.
  8. temperatureto warm to room temperature
  9. stirringstirring
  10. filtrationThe solution was filtered under vacuum
  11. washrinsed with water (360 mL)
  12. washThe filter cake is then washed with methyl tert-butyl ether (360 mL)
  13. customdried

Sources & evidence

ORD record
ord-e91d3bf1171543bb9b914ddc4c31d885
Source dataset
uspto-grants-2016_07
Patent number
US09388135B2

Reaction notes

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