N,N,N',N'-Tetramethylethylenediamine → 6-[2-(1-Aminoethyl)-4-methylphenyl]-4H-cyclopenta[b]-thiophene

Participants

Reaction Conditions

Reaction Steps

A solution of compound of Example 23 (3.7 g, 9.9 mmol) and N,N,N',N'-tetramethylethylenediamine (0.75 mL, 5.0 mmol) in dry ether (70 ml) was cooled to 0° C. and treated with a solution of n-BuLi (2.5M) in hexane (8.0 mL, 20.0 mmol). The mixture was stirred at 0° C. for 0.25 hour and then at room temperature for an additional 3 hours. At this point the mixture was cooled to -78° C. A solution of 4,5-dihydro-6H-cyclopenta[b]thiophen-6-one (1.40 g, 10.1 mmol) in dry THF (15 ml) was then added dropwise and the resulting mixture was stirred at -78° to -60° C. over 1 hour. The reaction was quenched by addition of saturated NH4Cl solution and was allowed to warm to room temperature. The mixture was diluted with ether and H2O. The ether layer was separated and concentrated to leave an oil which was taken up in a mixture of 1N HCl (70 mL) and THF (105 mL). The resulting solution was stirred at room temperature overnight. Following removal of most of the THF in vacuo, the solution was extracted twice with ether. The extracts were set aside for later recovery of unreacted 4,5-dihydro-6H-cyclopenta[b]-thiophen-6-one while the aqueous layer was made basic by addition of solid NaOH and extracted twice again with ether. These extracts were combined, dried (Na2SO4) and concentrated in vacuo to leave an oil. This was placed under high vacuum and warmed to remove α,4-dimethyl-benzenemethanamine. Following flash chromatography on silica gel using EtOAc as eluant, the title compound was isolated as an oil (180 mg, 7%).

Provenance & Evidence