Potassium Carbonate → 4-benzyloxy-1-(3-fluorobenzyl)-1H-pyridin-2-one

HRID 1867081Notes

Reaction equation

HRID 1867081 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[F:22][C:23]1[CH:24]=[C:25]([CH:28]=[CH:29][CH:30]=1)[CH2:26]Br>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([CH2:26][C:25]2[CH:28]=[CH:29][CH:30]=[C:23]([F:22])[CH:24]=2)[C:11](=[O:15])[CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 680073-Fluorobenzyl bromideHCID 36077244-Benzyloxy-2(1H)-pyridone

Product 1

HCID 220502224-benzyloxy-1-(3-fluorobenzyl)-1H-pyridin-2-oneYield 33%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A 100 mL round bottomed flask equipped with stirbar and nitrogen inlet was charged with 4-benzyloxy-2(1H)-pyridinone (20 g, 99.6 mmol) and N,N-dimethyl formamide (50 mL). K2CO3 (13.7 g, 99.6 mmol) and KI (1.6 g, 9.6 mmol) were added followed by 3-fluorobenzyl bromide (14.6 mL, 119.4 mmol). The reaction mixture was heated for 18 h at 80 C. The reaction mixture was concentrated in vacuo and treated with hot ethyl acetate. The solids were filtered off, the filtrate was poured into water and was extracted with ethyl acetate. The organic extract was washed with brine, dried with anhydrous Na2SO4, and concentrated in vacuo. The residue was dissolved in hot ethyl acetate and precipitated with hexanes to give the title compound (10 g, 33%). 1H NMR (400 MHz, CD3OD) δ 7.57 (d, J=8.4 Hz, 1H), 7.37 (m, 5H), 7.07 (d, J=8.4 Hz, 1H), 7.01 (app d, J=8.4 Hz, 2H), 6.17 (d, J=2.68 and 7.6 Hz, 1H), 6.04 (d, J=2.68 Hz, 1H), 5.10 (s, 2H), 5.08 (s, 2H) ppm. 19F NMR (400 MHz, CD3OD) δ −114.88 (1F) ppm. ES-HRMS m/z 310.1271 (M+H calcd for C19H17FNO2 requires 310.1238).

Workup

  1. customA 100 mL round bottomed flask equipped with stirbar and nitrogen inlet
  2. temperatureThe reaction mixture was heated for 18 h at 80 C
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. additiontreated with hot ethyl acetate
  5. filtrationThe solids were filtered off
  6. additionthe filtrate was poured into water
  7. extractionwas extracted with ethyl acetate
  8. extractionThe organic extract
  9. washwas washed with brine
  10. dry with materialdried with anhydrous Na2SO4
  11. concentrationconcentrated in vacuo
  12. dissolutionThe residue was dissolved in hot ethyl acetate
  13. customprecipitated with hexanes

Sources & evidence

ORD record
ord-83bdadd46a1e4a08b1e4d7e13a090fc1
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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