Trifluoroacetate → HCID 178484581, compound

Participants

Reaction Steps

To a solution of intermediate 2, 3-[2,3-dichloro-4-(pyrrolidin-1-ylmethyl)phenyl]-N,N-dimethylcyclobut-2-ene-1-carboxamide, trifluoroacetate (0.673 mmol) in 5 mL of ethanol was added chlorotris(triphenylphosphine)rhodium(I) (63 mg, 0.0673 mmol). The mixture was hydrogenated (40 psi H2, 50%) for 3 h; the reaction was monitored by LCMS. The mixture was evaporated to dryness, then 5 ml of 1 N HCl was added to the residue and the solution was extracted with ethyl acetate (2×5 ml), the organic layers were discarded. 10N NaOH (1 mL) was added to the water layer and the water solution was extracted with ethyl acetate (3×5 mL). The organic layers were dried and evaporated in vacuum. The residue was purified by chromatography (SiO2 63/100 μm, 10 g, CHCl3/hexane 80:20→100:0, CHCl3/MeOH 100:0→90:10). Fractions containing the product were evaporated. The residue was dissolved in 2 ml of ether and 0.1 mL of 4N HCl/dioxane was added under stirring. The mixture was evaporated; the residue was dried in vacuum to afford the title compound (74 mg, 28%) as a white solid. LCMS data: 355, 356, and 357 (M+H)+ (calculated for C18H24Cl2N2O 355.31). 1H NMR data (CD3OD): δ 7.69 (d, 1H, J=8.1 Hz), 7.58 (d, 1H, J=8.1 Hz), 4.62 (s, 2H), 3.88-3.98 (m, 1H), 3.54-3.63 (m, 2H), 3.35-3.45 (m, 1H), 3.25-3.34 (m, 2H+MeOH), 2.99 (s, 6H), 2.71-2.79 (m, 2H), 2.42-2.52 (m, 2H), 2.16-2.27 (m, 2H), 1.98-2.12 (m, 2H).

Provenance & Evidence