Triethylamine → N-(6-chloro-5-ethylpyridin-2-yl)pivalamide

HRID 2188895Notes

Reaction equation

HRID 2188895 reaction equation
CCN(CC)CC.[CH2:8]([C:10]1[CH:11]=[CH:12][C:13]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[N+:14]([O-:16])[CH:15]=1)[CH3:9].O=P(Cl)(Cl)[Cl:26]>>[Cl:26][C:15]1[N:14]=[C:13]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])[CH:12]=[CH:11][C:10]=1[CH2:8][CH3:9].[CH2:8]([C:10]1[CH:11]=[CH:12][C:13]([NH:17][C:18](=[O:23])[C:19]([CH3:22])([CH3:21])[CH3:20])=[N+:14]([O-:16])[CH:15]=1)[CH3:9]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178436613HCID 178436613, compound

Product 2

HCID 59272532N-(6-chloro-5-ethylpyridin-2-yl)pivalamideYield 5%HCID 178436613HCID 178436613, compound

Procedure

Et3N (123 mL, 93.6 mmol) was added to a solution of 5-ethyl-2-pivalamidopyridine 1-oxide (16.0 g, 72.0 mmol) in POCl3 (250 mL) and the reaction mixture was heated at reflux for 3 days. Excess POCl3 was distilled off and the residue was poured into water. The mixture was neutralized with aqueous NaOH to pH 9. The aqueous layer was extracted with EtOAc. The organic layer was dried over MgSO4 and the solvent was evaporated in vacuo. The residue was purified by chromatography on silica gel (10% EtOAc in petroleum ether) to afford N-(6-chloro-5-ethylpyridin-2-yl)pivalamide (900 mg, 5%) and unreacted 5-ethyl-2-pivalamidopyridine 1-oxide (4.8 g). 1H NMR (CDCl3, 300 MHz) δ 8.12 (d, J=8.7, 1H), 7.94 (br s, 1H), 7.56 (d, J=8.7, 1H), 2.70 (q, J=7.5, 2H), 1.30 (s, 9H), 1.23 (t, J=7.5, 3H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux for 3 days
  3. distillationExcess POCl3 was distilled off
  4. additionthe residue was poured into water
  5. extractionThe aqueous layer was extracted with EtOAc
  6. dry with materialThe organic layer was dried over MgSO4
  7. customthe solvent was evaporated in vacuo
  8. customThe residue was purified by chromatography on silica gel (10% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-acffd23ed22746038f0c37ebc664f6ee
Source dataset
uspto-grants-2012_12
Patent number
US08324207B2

Reaction notes

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