p-Toluenesulfonic acid → HCID 13720637, compound

Participants

Reaction Conditions

Reaction Steps

A solution of 4-(1,1-dimethylpropoxy)-1-(pyrid-2-yl)-butan-1-ol (122 g) and para-toluenesulphonic acid (107.4 g) in toluene (1000 cc) is kept at the boil for 28 hours so that the water formed is removed by azeotropic distillation. After cooling to a temperature of about 20° C., distilled water (250 cc) is added. The organic phase is decanted and washed with distilled water (50 cc); the aqueous phases are combined and neutralised by adding sodium bicarbonate (49 g). The mixture is extracted three times with ethyl acetate (1500 cc in total). The organic extracts are combined and filtered and the filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. A first oily fraction (30.8 g) is thus obtained. The aqueous phase previously obtained is re-extracted five times with methylene chloride (2500 cc in total); the organic extracts are combined, dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 35° C. A second oily fraction (11.2 g) is thus obtained. The two fractions (30.8 g and 11.2 g) are combined and run into polyphosphoric acid (200 g) at 80° C., in the course of 30 minutes. After stirring for 10 minutes at the same temperature and then cooling to a temperature of about 20° C., the reaction mixture is poured into distilled water (400 cc). A 10 N aqueous solution of sodium hydroxide (450 cc) is then added, whilst keeping the temperature below 20° C. The resulting crystals are filtered off and washed with ethyl acetate (500 cc). After separation of the filtrate by decantation, the aqueous phase is extracted three times with ethyl acetate (1500 cc in total). The organic extracts are combined, dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. 2-(Pyrid-2-yl)-tetrahydrofuran (26 g) is thus obtained.

Provenance & Evidence