Trifluoroacetic anhydride → 4-cyano-3-(methoxycarbonyl)-2-(1-methyl-1H-pyrazol-4-yl)pyridine 1-oxide

HRID 711459Notes

Reaction equation

HRID 711459 reaction equation
[C:1]([C:3]1[C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([C:13]2[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=2)[N:6]=[CH:5][CH:4]=1)#[N:2].NC(N)=[O:21].OO.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)Cl.C(Cl)(Cl)Cl>[C:1]([C:3]1[CH:4]=[CH:5][N+:6]([O-:21])=[C:7]([C:13]2[CH:14]=[N:15][N:16]([CH3:18])[CH:17]=2)[C:8]=1[C:9]([O:11][CH3:12])=[O:10])#[N:2]

Participants

7

Reactant 4

HCID 9845Trifluoroacetic anhydrideHCID 31294Carbamide Peroxide2×HCID 516892Sodium BicarbonateHCID 58317645Methyl 4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate

Product 1

HCID 672387104-cyano-3-(methoxycarbonyl)-2-(1-methyl-1H-pyrazol-4-yl)pyridine 1-oxide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of methyl 4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (470 mg, 1.940 mmol) in DCM (10 mL) was added urea-hydrogen peroxide compound (1/1, 913 mg, 9.70 mmol), and 2,2,2-trifluoroacetic anhydride (1.370 mL, 9.70 mmol) at 0° C. The mixture was stirred at room temperature for 4 h. More urea-hydrogen peroxide compound (1/1, 400 mg) was added and the mixture was stirred at RT for an additional 3 h after which was added saturated aq NaHCO3 solution and CHCl3. The aqueous phase was extracted with CHCl3 (3×), and the combined organic layers were washed with brine, dried over MgSO4, and evaporated to obtain crude 4-cyano-3-(methoxycarbonyl)-2-(1-methyl-1H-pyrazol-4-yl)pyridine 1-oxide, which was combined with phosphorus oxychloride (2 mL, 21.46 mmol). The resulting mixture was stirred at 80° C. for 5 h and then concentrated to a residue, which was neutralized with 2N NaOH. The organic phase was washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2(Hexane/EtOAc=1/1) to give the title compound as a white solid (155 mg, 41.3%). 1H NMR (500 MHz, CDCl3) δ ppm 3.96 (s, 3H), 4.03 (s, 3H), 7.41 (s, 1H), 7.81 (s, 1H), 7.94 (s, 1H). [M+H] calc'd for C12H9ClN4O2, 277. found, 277.

Workup

  1. stirringthe mixture was stirred at RT for an additional 3 h after which
  2. extractionThe aqueous phase was extracted with CHCl3 (3×)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated

Sources & evidence

ORD record
ord-4e86a97ba450433e98c677f36065a708
Source dataset
uspto-grants-2015_11
Patent number
US09181255B2

Reaction notes

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