Hydrogen Peroxide → 4-Chloro-N-methylpicolinamide

Temperatur

60 °C

Caution: this is a highly hazardous, potentially explosive reaction. To a stifling solution of 4-chloropyridine (10.0 g) in N-methylformamide (250 mL) at room temp. was added conc. H2SO4 (3.55 mL) to generate an exotherm. To this mixture was added H2O2 (30% wt in H2O, 17 mL) followed by FeSO4.7H2O (0.56 g) to generate another exotherm. The resulting mixture was stirred in the dark at room temp. for 1 h, then warmed slowly over 4 h to 45° C. When bubbling had subsided, the reaction was heated at 60° C. for 16 h. The resulting opaque brown solution was diluted with H2O (700 mL) followed by a 10% NaOH solution (250 mL). The resulting mixture was extracted with EtOAc (3×500 mL). The organic phases were washed separately with a saturated NaCl solution (3×150 mL), then they were combined, dried (MgSO4) and filtered through a pad of silica gel with the aid of EtOAc. The resulting brown oil was purified by column chromatography (gradient from 50% EtOAc/50% hexane to 80% EtOAc/20% hexane). The resulting yellow oil crystallized at 0° C. over 72 h to give 4-chloro-N-methyl-2-pyridinecarboxamide (0.61 g, 5.3%): TLC (50% EtOAc/50% hexane) Rf 0.50; 1H NMR (CDCl3) δ 3.04 (d, J=5.1 Hz, 3H), 7.43 (dd, J=5.4, 2.4 Hz, 1H), 7.96 (br s, 1H), 8.21 (s, 1H), 8.44 (d, J=5.1 Hz, 1H); CI-MS m/z 171 ((M+H)+).

1. custompotentially explosive reaction
2. temperaturewarmed slowly over 4 h to 45° C
3. customWhen bubbling
4. additionThe resulting opaque brown solution was diluted with H2O (700 mL)
5. extractionThe resulting mixture was extracted with EtOAc (3×500 mL)
6. washThe organic phases were washed separately with a saturated NaCl solution (3×150 mL)
7. dry with materialdried (MgSO4)
8. filtrationfiltered through a pad of silica gel with the aid of EtOAc
9. customThe resulting brown oil was purified by column chromatography (gradient from 50% EtOAc/50% hexane to 80% EtOAc/20% hexane)
10. customThe resulting yellow oil crystallized at 0° C. over 72 h

ORD-Eintrag

ord-7a1be62929e74c5791e40991e7816676

Quelldatensatz

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08841330B2