Water → HCID 68183323, compound

Participants

Reaction Conditions

Reaction Steps

A 100 mL rbf was charged with a solution of ethyl 3-[3-amino-1-(4-chlorophenyl)propyl]-5-(morpholin-4-yl)thiophene-2-carboxylate.TFA (842 mg, 1.61 mmol) in ethanol (10.0 mL) and 21% sodium ethoxide (21:79, Sodium ethoxide: ethanol, 4.81 mL, 12.9 mmol). The rbf was equipped with a reflux condenser and the reaction was heated to 80° C. In 3 h, the solution was cooled and distributed between water and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined org layer was washed with brine (×2), dried, and concentrated to provide a yellow solid. Purification on a silica gel column (continuous gradient from CH2Cl2 to 8% MeOH/CH2Cl2) provided 420 mg of 4-(4-chlorophenyl)-2-(morpholin-4-yl)-4,5,6,7-tetrahydro-8H-thieno[2,3-c]azepin-8-one as a yellow solid (71.9% yield). LCMS: (AA) ES+ 363, 365; 1H NMR (400 MHz, DMSO-d6) δ 7.81-7.71 (s, 1H), 7.41-7.32 (m, 2H), 7.18-7.09 (m, 2H), 5.64-5.55 (s, 1H), 4.38-4.27 (dd, J=7.9, 5.1 Hz, 1H), 3.70-3.58 (t, J=4.9 Hz, 4H), 3.14-3.06 (d, J=4.3 Hz, 2H), 3.06-2.96 (t, J=4.9 Hz, 4H), 2.24-2.13 (m, 1H), 2.03-1.90 (m, 1H). Racemic 4-(4-chlorophenyl)-2-(morpholin-4-yl)-4,5,6,7-tetrahydro-8H-thieno[2,3-c]azepin-8-one (0.42 g) was separated into enantiomers on a Chiralpak IA 30×250 mm 5 micron column using a 60/40/0.1 Hexane-EtOH-DEA mixture and a flow rate of 35 mL/min. Peak one (195 mg) was collected with retention times of 10-18 min and peak two (208 mg) was collected with retention times of 26.5-38.5 min. Absolute configuration of the obtained enantiomers is unknown.

Provenance & Evidence