Potassium Iodide → HCID 21471883, compound

Participants

Reaction Steps

A mixture of 0.5 g of 2-((3-chloropropyl)thio)-4-oxo-4,5,6,7-tetrahydrobenzo(b)thiophene, 0.5 g of 4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidine hydrochloride, 0.6 g of potassium carbonate and 0.4 g of potassium iodide in 10 ml of dimethylformamide and 10 ml of toluene was mixed at 100° C. for 4 hours and poured into water. The toluene layer was washed with water, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on a silica gel to give 0.5 g of 2-(3-(4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl)propylthio)-4-oxo-4,5,6,7-tetrahydrobenzo(b)-thiophene. The resulting compound was dissolved in 20 ml of ethanol, and 0.1 g of hydroxylamine hydrochloride and 0.12 g of sodium hydrogencarbonate were added thereto. After the mixture was refluxed for 3 hours, the solvent was distilled away in vacuo and water was added to the residue, and then extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated. To the residue was added isopropyl ether to give 0.5 g of an oxime compound as crystals. A mixture of 0.35 g of the oxime compound and 3.5 g of 115% polyphosphoric acid was stirred at 100° C. for 5 hours, poured into water and extracted with chloroform. The extract was washed with water, dried and concentrated. The residue was separated and purified by column chromatography on a silica gel and each of resulting crystals was recrystallized from isopropyl ether to give 0.06 g of 2-(3-(4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl)propylthio)-5,6,7,8-tetrahydro-4H-thieno[3,2-c]azepin-4-one, m.p. 119°-121° C. and 0.019 g of 2-(3-(4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl)propylthio)-4,6,7,8-tetrahydro-5H-thieno[3,2-b]azepin-5-one, m.p. 125°-127° C.

Provenance & Evidence