Water → 1-Benzothiophen-3-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of methyl 3-aminobenzothiophene-2-carboxylate [prepared by the method of J. R. Beck, J. Org. Chem. 1972, 37, 3224] (6.5 g, 31.4 mmol) in N-methylpyrrolidinone (30 ml) was added 1-methylpiperazine and the reaction mixture was heated to 178° C. for 4 h. After cooling the mixture was poured into water and the product extracted with diethyl ether (3×100 ml), the extracts were washed with water (1×100 ml) and brine (1×100 ml), combined and dried (MgSO4). Concentration of the extracts yielded 3-aminobenzothiophene (5.9 g), which was used without purification. To a solution of 3-aminobenzothiophene (5 g, 32 mmol) in N-methylpyrrolidinone (50 ml) was added piperazine (8.7 g, 102 mmol) and the mixture heated to reflux under nitrogen for 14 h. Cooled and poured into water and extracted with dichloromethane (4×100 ml). The extracts were washed with brine (50 ml), combined and dried (MgSO4). On concentration of the extracts a white solid came out of solution which was collected by filtration to yield the title compound (0.78 g, more product left in solution); δH (DMSO-d6 +(TFA), 3.3 (3H, m, 4×piperazinyl CH2), 7.08 (1H, s, 3-H), 7.39 (2H, m, 2×ArH), 7.83 (1H, m, ArH), 7.95 (1H, m, ArH), and 9.30 (1H, br s, NH).

Provenance & Evidence