Water → HCID 19360250, compound

Participants

Reaction Steps

A solution of 3-amino-5-trifluoromethylbenzo[b]thiophene (27 g, 124 mmol) and 4-chloropyridine hydrochloride (20.5 g, 137 mmol) in 250 mL of 1-methyl-2-pyrrolidinone was stirred at 70-80° C. for 1.5 hours. After cooling, the reaction mixture was stirred with water, washed with ether and separated. The aqueous layer was basified with a saturated sodium carbonate solution and the product which precipitated was collected. The reaction was repeated as above with an additional sample of 3-amino-5-trifluoromethylbenzo[b]thiophene (25.6 g, 118 mmol) and 4-chloropyridine hydrochloride (22 g, 148 mmol) in 225 mL of 1-methyl-2-pyrrolidinone. After a similar work-up, the two products were combined and dissolved in 10% methanol in ethyl acetate. The solution was dried (anhydrous magnesium sulfate), filtered and concentrated, yielding a yellow solid. This solid product was washed with ether and filtered to afford 39.1 g of a golden solid. Elution of a portion (3.5 g) of the residue through silica with ethyl acetate via flash column chromatography afforded 3.2 g of a white solid. Conversion of 2.4 g to the hydrochloride salt in 10% methanol in ether afforded 2.6 g of white crystals, mp 318-319° C.

Provenance & Evidence