Methane → HCID 13711421, compound

Participants

Reaction Steps

To a 1.6M solution (3,150 cc) of n-butyllithium in hexane maintained under an atmosphere of nitrogen at between -65° and -70° C., a mixture (1,680 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) is added slowly, followed by a solution of 3-chloropropyl(6-methyl-2-pyridyl)methyl ether (360 g) in a mixture (1,080 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) added dropwise in the course of 1 hour. After 5 minutes' stirring, a solution of methyl isothiocyanate (158 g) in a mixture (432 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) is added in the course of 35 minutes. The mixture is stirred for 1 hour at -60° C. and distilled water (4,800 cc) is then added slowly, the temperature being allowed to rise to about 20° C. The mixture is stirred for 5 minutes and then extracted with ethyl acetate (2,400 cc). The aqueous phase is decanted and extracted 4 times with ethyl acetate (6,000 cc in total). The organic liquors are combined, washed twice with aqueous sodium chloride solution (1,800 cc in total) at a concentration of 180 g per liter, and then extracted 3 times with 2N aqueous hydrochloric acid solution (4,500 cc in total). The acidic aqueous extracts are combined, washed twice with diethyl ether (3,000 cc in total) and then brought to a pH in the region of 8 using 10N aqueous sodium hydroxide solution. The mixture is extracted 4 times with ethyl acetate (10 liters in total). The organic extracts are combined, washed twice with distilled water (3.6 liters in total), dried over anhydrous magnesium sulphate in the presence of decolorising charcoal (18 g) for 1 hour and then filtered. The filtrate is concentrated to a small volume under reduced pressure (30 mm Hg; 4 kPa) at a temperature in the region of 35° C. The crystallised product is separated by filtration, washed with isopropanol (180 cc) and dried in a stream of air. The product obtained (118 g) is dissolved in boiling absolute ethanol (472 cc). To the solution is added decolorising charcoal (1 g), and the mixture is filtered hot. The filter is washed with a little boiling ethanol, and the solution is then cooled in an ice bath for 1 hour. The crystals which appear are separated by filtration, washed with ice-cooled absolute ethanol (120 cc) and dried in a stream of air at 20° C. N-Methyl-2-(6-methyl-2-pyridyl)-2-tetrahydrofurancarbothioamide (110 g), m.p. 151.4° C., is thereby obtained.

Provenance & Evidence