Potassium Acetate → 4-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

HRID 1866971Notes

Reaction equation

HRID 1866971 reaction equation
[F:1][C:2]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][N+:9]([O-])=[CH:8][CH:7]=1.C([O-])(=[O:20])C.[K+].CC(OCC1C2C(=CC=CC=2)C(COC(C)=O)=C2C=1C=CC=C2)=O>C(O)(=O)C>[F:1][C:2]1[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][NH:9][C:8](=[O:20])[CH:7]=1

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 613145Acetic acid 10-acetoxymethyl-anthracen-9-ylmethyl esterHCID 220502194-(2,4-Difluorobenzyloxy)pyridine-1-oxide

Product 1

HCID 220503904-(2,4-difluorobenzyloxy)-1H-pyridin-2-one

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
130 °C

Procedure

4-[(2,4-difluorobenzyl)oxy]pyridine 1-oxide (from Step 1) (30.0 g, 0.127 mol), anhydrous potassium acetate (25 g, 0.25 mol), acetic anydride (25 g, 0.25 mol), and 10 ml acetic acid were combined in a 250-ml round-bottomed flask with overhead stirring and heated to 130° C. for 4 hours. The mixture was concentrated under vacuum, the solids dissolved in 95 ml acetonitrile; 5 ml water, filtered through charcoal and poured into 600 ml ice with stirring. The mixture was allowed to stand overnight at room temperature, then 9.62 g (30%) product collected by filtration as a medium brown solid (adequate for the next step without purification). 1H-NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 7.59 (quartet, J=9.91 Hz, 1H), 7.29 (t, J=10.36 Hz, 1H), 7.21 (d, J=8.20 Hz, 1H), 7.11 (t, J=8.48 Hz, 1H), 5.83 (m, 2H), 5.02 (s, 2H). 19F-NMR (400 MHz, DMSO-d6) δ −109.57 (quintet, J=7.66 Hz, 1F)-113.88 (quartet, J=8.93 Hz, 1F). LC/MS tr=4.29 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50° C.) ES-MS m/z 238 (M+H).

Workup

  1. concentrationThe mixture was concentrated under vacuum
  2. dissolutionthe solids dissolved in 95 ml acetonitrile
  3. filtration5 ml water, filtered through charcoal
  4. additionpoured into 600 ml ice
  5. stirringwith stirring
  6. filtration9.62 g (30%) product collected by filtration as a medium brown solid (adequate for the next step
  7. customwithout purification)
  8. customLC/MS tr=4.29 minutes (0-95% acetonitrile/water, 0.05% trifluoroacetic acid, over 6 minutes at 1 ml/min with detection at 254 nm, at 50° C.) ES-MS m/z 238 (M+H)

Sources & evidence

ORD record
ord-4627671bf36248509e690db054ca3b77
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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