Trifluoromethanesulfonic anhydride → 6-Chloro-3-cyano-2-(4-nitro-phenoxycarbonylmethyl)-pyridine 1-oxide

HRID 1171063Notes

Reaction equation

HRID 1171063 reaction equation
C([O-])([O-])=[O:2].C([O-])([O-])=O.OO.OO.OO.[Na+].[Na+].[Na+].[Na+].[N+:19]([C:22]1[CH:27]=[CH:26][C:25]([O:28][C:29](=[O:40])[CH2:30][C:31]2[C:36]([C:37]#[N:38])=[CH:35][CH:34]=[C:33]([Cl:39])[N:32]=2)=[CH:24][CH:23]=1)([O-:21])=[O:20].S(OS(C(F)(F)F)(=O)=O)(C(F)(F)F)(=O)=O.C([O-])(O)=O.[Na+]>CC#N.CCOC(C)=O.C(Cl)Cl>[Cl:39][C:33]1[N+:32]([O-:2])=[C:31]([CH2:30][C:29]([O:28][C:25]2[CH:26]=[CH:27][C:22]([N+:19]([O-:21])=[O:20])=[CH:23][CH:24]=2)=[O:40])[C:36]([C:37]#[N:38])=[CH:35][CH:34]=1

Participants

8

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 159762Sodium percarbonateHCID 516892Sodium BicarbonateHCID 58972958(6-chloro-3-cyano-pyridin-2-yl)-acetic Acid 4-nitro-phenyl Ester

Product 1

HCID 589729596-Chloro-3-cyano-2-(4-nitro-phenoxycarbonylmethyl)-pyridine 1-oxide

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Solid sodium percarbonate (555 mg, 5.30 mmol H2O2) (Na2CO3.1.5 H2O2, approximately 25% H2O2, Aldrich) was added in one portion under air with stirring to a rt solution of (6-chloro-3-cyano-pyridin-2-yl)-acetic acid 4-nitro-phenyl ester (566 mg, 1.78 mmol), as prepared in the previous step, in CH3CN (13.5 mL) and the slurry was then stirred on an ice bath for 5-10 min. The flask was fitted with an argon needle outlet to prevent pressure build-up, and triflic anhydride (7.58 g, 26.9 mmol) was added dropwise with stirring at 0° C. over about 4 min. The reaction was stirred at 0° C. for 3.5 h, and was then poured into 0° C. saturated NaHCO3 (80 mL), with the residual yellow reaction mixture transferred with DCM (2×10 mL). The ice-cold bilayer was stirred at 0° C. for 30 min, and the light yellow organic layer was saved. The dark yellow upper aqueous layer was extracted with DCM (2×40 mL), the organic layers were combined, dried (Na2SO4), and concentrated to provide 463 mg of the crude title compound as a tan solid. This material was combined with a separately-prepared batch of crude title compound (250 mg), and the whole was dissolved in EtOAc (˜20 mL) and concentrated under reduced pressure in the presence of silica gel (2.7 g) to afford a free-flowing powder. This silica-adsorbed material was flash chromatographed (2:1 toluene/EtOAc eluent) to afford the title compound as a beige solid [319 mg, 35% (calculated from the 463 mg crude)].

Workup

  1. customThe flask was fitted with an argon needle outlet
  2. stirringwith stirring at 0° C. over about 4 min
  3. stirringThe reaction was stirred at 0° C. for 3.5 h
  4. extractionThe dark yellow upper aqueous layer was extracted with DCM (2×40 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customto provide 463 mg of the crude title compound as a tan solid
  8. concentrationconcentrated under reduced pressure in the presence of silica gel (2.7 g)
  9. customto afford a free-flowing powder
  10. customchromatographed (2:1 toluene/EtOAc eluent)

Sources & evidence

ORD record
ord-4a36d29e883a46f5b8cf747cf0af3639
Source dataset
uspto-grants-2010_11
Patent number
US07829584B2

Reaction notes

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