Iodine → HCID 68183132, compound

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of 4-(3,4-dichlorophenyl)-4,5,6,7-tetrahydro-8H-thieno[2,3-c]azepin-8-one (1.05 g, 3.36 mmol) in tetrahydrofuran (30 mL) at −78° C. was added a solution of n-butyllithium in hexane (2.5 M, 6.73 mL, 16.82 mmol) in rapid drops under an atmosphere of argon. The reaction solution became purplish after ˜2 ml had been added and became intensely purple by the end of the addition. The reaction solution was stirred at −78° C. for 30 minutes then iodine (7.95 g, 31.3 mmol) was added as a solid in a single portion with good stirring—the purple color was instantly quenched to give a reddish brown mixture. The resulting mixture was stirred at −78° C. for 5 minutes then the dry ice/acetone bath was removed and the reaction was allowed to warm to rt with stirring for one hour. A saturated sodium bisulfate solution (150 mL) was added to the reaction mixture with good stirring—most of the color faded to give a lemon yellow mixture. Ethyl acetate was added and the mixture was transferred to a separatory funnel. The organic layer was separated, the aqueous layer was extracted with ethyl acetate, the combined organic layers were washed with saline, dried over sodium sulfate, filtered, and concentrated to leave crude product as a light orange solid. The crude product was stirred with DCM—most solids did not dissolve. The mixture was sonicated well, diluted with t-butyl methyl ether, and the white precipitate was isolated on a fritted funnel. It was washed it with additional TBME and air-dried to leave 787 mg product as a white powder. The filtrate was evaporated to leave an orange residue which was purified using column chromatography on silica gel (80 g RediSep column, gradient 0% ethyl acetate in hexane to 100% ethyl acetate in hexane over 30 minutes) to give 440 mg additional product as a white solid. Total yield 1.227 g (83% yield). LCMS: (FA) ES+ 438, 440. 1H NMR (400 MHz, DMSO) δ 8.27-8.20 (d, J=4.5 Hz, 1H), 7.61-7.53 (d, J=8.3 Hz, 1H), 7.47-7.42 (d, J=2.0 Hz, 1H), 7.09-7.02 (dd, J=8.3, 2.1 Hz, 1H), 6.81-6.75 (s, 1H), 4.51-4.41 (dd, J=8.6, 5.3 Hz, 1H), 3.22-3.05 (d, J=5.5 Hz, 2H), 2.27-2.14 (m, 1H), 2.09-1.99 (m, J=7.9 Hz, 1H).

Provenance & Evidence