Formic Acid → 2-Oxo-5-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile

HRID 132840Notes

Reaction equation

HRID 132840 reaction equation
[CH:1]([C:3]1[C:4]([OH:13])=[N:5][CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1)=O.C([O-])=O.[Na+].Cl.[NH2:19]O.C(O)=O>O>[C:1]([C:3]1[C:4]([OH:13])=[N:5][CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1)#[N:19]

Participants

6

Reactant 4

HCID 284Formic AcidHCID 443297Hydroxyamine hydrochlorideHCID 2723810Sodium FormateHCID 198196692-Oxo-5-(trifluoromethyl)-1,2-dihydropyridine-3-carbaldehyde

Product 1

HCID 148370202-Oxo-5-(trifluoromethyl)-1,2-dihydropyridine-3-carbonitrile

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of the compound from Step B above (18 g, 95 mmol), sodium formate (7.1 g, 110 mmol), hydroxylamine hydrochloride (7.3 g, 110 mmol), and formic acid (150 mL) was stirred at room temperature for 2 h and then heated to reflux overnight. The reaction mixture was cooled, allowed to stand at room temperature for 7 d, poured into water and extracted with three portions of ethyl acetate. The combined organic layers were washed sequentially with two portions of water, saturated aqueous sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated in vacuo to yield the desired product as a brown powder. 1H NMR (400 MHz, CD3OD) δ 8.37 (d, J=2.7 Hz, 1H), 8.19 (q, J=0.7 Hz, 0.3 Hz, 1H).

Workup

  1. temperatureheated
  2. temperatureto reflux overnight
  3. temperatureThe reaction mixture was cooled
  4. waitto stand at room temperature for 7 d
  5. extractionextracted with three portions of ethyl acetate
  6. washThe combined organic layers were washed sequentially with two portions of water, saturated aqueous sodium bicarbonate solution and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a90803229e1048bd8eb8e095c822d434
Source dataset
uspto-grants-2008_06
Patent number
US07388019B2

Reaction notes

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