Hydrochloric Acid → 2-Chloro-[1,3]thiazolo[5,4-b]pyridine

Participants

Reaction Conditions

Reaction Steps

3-Amino-2-bromopyridine (1.14 g, 6.59 mmol) and ethyl potassium xanthate (2.324 g, 14.50 mmol) were dissolved in dry dimethylformamide (4 mL) and heated at 130° C. for 15 hours. The reaction was cooled and diluted with water (150 mL). 5 N Hydrochloric acid (4 mL) was added and the mixture stirred. The intermediate precipitated as a light yellow solid and was filtered off. The solids were suspended in warm ethyl acetate (200 mL) and dried with magnesium sulfate. The filter cake was washed with additional warm ethyl acetate (200 mL). The organic was evaporated to dryness under reduced pressure and suspended in dichloromethane (50 mL). Sulfuryl chloride (20 ml, 247 mmol) was added and the mixture stirred at room temperature. After 1 hour, the mixture was evaporated to dryness under reduced pressure and the residue partitioned between ethyl acetate (200 mL), ice (˜50 mL), water (100 mL) and saturated sodium bicarbonate (60 mL). The organic phase was dried with magnesium sulfate and evaporated to dryness under reduced pressure. Purification using silica chromatography (dichloromethane to ethyl acetate gradient) gave the desired 2-chlorothiazolo[5,4-b]pyridine (0.120 g, 0.703 mmol, 10.7% yield).

Provenance & Evidence