HCID 22049899, compound → HCID 22050069, compound

HRID 1867057Notes

Reaction equation

HRID 1867057 reaction equation
[Br:1][C:2]1[C:3](=[O:28])[N:4]([C:20]2[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:21]=2[F:27])[C:5]([CH2:18][OH:19])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].CC(C)=[O:31].OS(O)(=O)=O.O=[Cr](=O)=O>CC(C)=O>[Br:1][C:2]1[C:3](=[O:28])[N:4]([C:20]2[C:21]([F:27])=[CH:22][CH:23]=[CH:24][C:25]=2[F:26])[C:5]([C:18]([OH:31])=[O:19])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

4

Reactant 2

HCID 22049899HCID 22049899, compoundHCID 131709961Jones' reagent

Product 1

HCID 22050069HCID 22050069, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 100 ml round bottom flask, 3-bromo-4-[(2,4-difluorobenzyl)oxy]-1-(2,6-difluorophenyl)-6-(hydroxymethyl)pyridin-2(1H)-one (1.70 g, 3.7 mmol) was dissolved in acetone (10 mL) and cooled to 0° C. in ice bath. To the reaction was added 1M acetone solution of Jones (5 ml, excess amount). Additional Jones reagent was added over time (approximately 6 hours) until the reaction was complete. The reaction was then concentrated down to dryness. The residue was then taken up in ethyl acetate (10 mL) and washed with brine. The dark yellow to brown colored crude product was purified by dissolving in 1N aqueous NaOH. The remaining organic impurities were removed by extracting with diethyl ether. The organic layers were discarded and the aqueous layer was acidified with dilute HCl (til pH app 1) to precipitate the pure acid which was then filtered and triturated with ether to obtain 1.17 g (65%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 7.66 (q, J=9.41 Hz, 1H), 7.57-7.50 (m, 1H), 7.34 (dt, J=10.11, 2.78 Hz, 1H), 7.28-7.23 (m, 3H), 7.18 (dt, 8.90, 2.42 Hz, 1H), 5.47 (s, 2H). ES-HRMS m/z 471.9814 (M+H calcd for C19H11BrF4NO4, requires 471.9808)

Workup

  1. concentrationThe reaction was then concentrated down to dryness
  2. washwashed with brine
  3. customThe dark yellow to brown colored crude product was purified
  4. dissolutionby dissolving in 1N aqueous NaOH
  5. customThe remaining organic impurities were removed
  6. extractionby extracting with diethyl ether
  7. customto precipitate the pure acid which
  8. filtrationwas then filtered
  9. customtriturated with ether

Sources & evidence

ORD record
ord-541ca7715a9f4d87945bf0151afbc916
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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