Ammonium Hydroxide → 4-Chloro-2,6-dimethylpyridine

A mixture of 2,6-lutidine-N-oxide hydrochloride (48 g) and phosphorus oxychloride (110 ml) is heated 6.5 hours at reflux. After cooling the reaction mixture is carefully poured into crushed ice (1 kg). While the temperature is maintained below 15° C., concentrated ammonium hydroxide is added up to reach pH 8. The product that separates is extracted with ethyl ether (2×500 ml) which is dried and distilled off. The residue is dissolved in ethanol (400 ml) and boiled 3 hours with triethylamine (20 ml). After cooling, the solution is evaporated to dryness, treated with water (200 ml) and extracted with ethyl ether (4×150 ml). The combined extracts are dried and the solvent evaporated. The residue after distillation gives 4-chloro-2,6-dimethylpyridine (25 g), b.p. (15 mm)=67°-69° C. To a mixture of sodium (10 g, 30% dispersion in toluene) in anhydrous dimethyoxyethane (40 ml) cooled in an ice-bath and kept under argon, trimethyltin chloride (12.1 g) in dimethoxymethane (6 ml) is added over a one hour period while keeping the temperature at 0° C. The mixture is stirred 2.5 hours at 0° C.; then 4-chloro-2,6-dimethylpyridine (7 g) in dimethoxyethane is slowly dropped into. Stirring is continued for an additional hour then the reaction mixture is allowed to stand overnight at room temperature. The reaction mixture is diluted with ethyl ether (100 ml) and filtered. The solvent is evaporated, the residue dissolved in ethyl ether (100 ml) and filtered again. After evaporation of the solvent the residue is distilled giving 2,6-dimethyl-4-(trimethyl-stannyl)pyridine (8.8 g), b.p. (15 m)=130°-140° C.

1. temperatureis heated 6.5 hours
2. temperatureat reflux
3. temperatureAfter cooling the reaction mixture
4. additionis carefully poured
5. temperatureWhile the temperature is maintained below 15° C.
6. extractionThe product that separates is extracted with ethyl ether (2×500 ml) which
7. customis dried
8. distillationdistilled off
9. dissolutionThe residue is dissolved in ethanol (400 ml)
10. temperatureAfter cooling
11. customthe solution is evaporated to dryness
12. additiontreated with water (200 ml)
13. extractionextracted with ethyl ether (4×150 ml)
14. customThe combined extracts are dried
15. customthe solvent evaporated
16. distillationThe residue after distillation

ORD record

ord-ad24f394629f4cd488c1bac34fe74860

Source dataset

uspto-grants-1998_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05786350