Trifluoroacetate → HCID 178461409, compound

Participants

Reaction Steps

To a solution of Intermediate 6, (2R)-1-{2-chloro-4-[3-(pyrrolidin-1-ylcarbonyl)cyclobut-1-en-1-yl]benzyl}-2-methylpyrrolidine, trifluoroacetate (1.06 mmol) in 5 mL of ethanol was added chlorotris(triphenylphosphine)rhodium(I) (100 mg, 0.106 mmol). The mixture was hydrogenated (40 psi H2, at 50° C.) 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 vacuo. The residue was purified by chromatography (SiO2 63/100 μm, 10 g, CHCl3/hexane 80:20→100:0, CHCl3/MeOH 100:0→90:10). The product containing fractions were collected and concentrated under reduced pressure. The residue was dissolved in 2 ml of ether and 0.1 mL of 4N HCl/dioxane was added under stirring. The solvent was evaporated; the residue was dried in vacuum to afford the HCl salt of the title compound (80 mg, 20%) as a dark yellow amorphous solid. LCMS data: 361 and 363 (M+H)+ (calculated for C21H29ClN2O 360.93). 1H NMR data (CD3OD): δ 7.63 (d, 1H, J=7.5 Hz), 7.50 (s, 1H), 7.39 (d, 1H, J=7.5 Hz), 4.75 (d, 1H, J=13.3 Hz), 4.31 (d, 1H, J=13.3 Hz), 3.63-3.77 (m, 2H), 3.34-3.52 (m, 7H), 2.64-2.75 (m, 2H), 2.33-2.49 (m, 3H), 1.72-2.20 (m, 7H), 1.51 (d, 3H, J=6.3 Hz).

Provenance & Evidence