Hydrochloric Acid → 1,2,3,4-Tetrahydro-benzo(b)azepin-5-one

Participants

Reaction Conditions

Reaction Steps

Compound 71 (1.75 g, 13.0 mmol) was dissolved in 40 mL of dry Et2O under N2 and the solution was cooled to 40° C. nBuLi (2.5 M solution in hexane, 5.7 mL, 14.3 mmol) was added and the reaction mixture was allowed to warm up to 0° C. during 1 h and then sulfur (0.414 g, 13.0 mmol) was added in one portion. The solution was allowed to slowly warm up to RT over 3 h. Excess of 10% HCl was added and the reaction mixture was stirred for 20 min. The thiol was extracted with ether, washed with brine, dried over Na2SO4 and concentrated to afford 2.0 g of crude compound 72 which was used in the next step without further purification. 2-(Benzo[b]thiophen-2-ylthio)-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (73): Crude compound 72 (0.71 g, 4.3 mmol) was dissolved in 40 mL of dry THF under N2, stirred for 30 min at RT and then cooled down to 0° C. NaH (60% in mineral oil, 0.224 g, 5.5 mmol) was added to the ice-cold solution which became a yellowish suspension. The formed suspension was stirred for 40 min at 0° C. and then 2-chloro-1-(3,4-dihydroquinolin-1(2H)-yl)ethanone (0.89 g, 4.3 mmol) was added as a solution in 4 mL of dry THF. The reaction mixture was stirred at RT for 16 h. The work-up, the same as for compound 5, gave crude material which was purified by flash chromatography (CH2Cl2/EtOAc) giving 0.56 g of the crude product. Pumping the crude product under high vacuum over P4O10 at 45° C. for 4 h removed the co-crystallized EtOAc to yield the desired product 73 (36%): MS: m/z+ 340.1 [M+H]+; Anal. Calcd (found) for C19H17NOS2: C, 67.22; (67.18), H, 5.05; (5.11), N, 4.13; (4.08), S, 18.89; (18.70).

Provenance & Evidence