Trifluoroacetic acid → HCID 118114112, compound

Participants

Reaction Steps

To a mixture of (S)-methyl 1-((4-((3-((S)-((tert-butoxycarbonyl)amino)(phenyl)-methyl)-phenoxy)methyl)phenyl)-sulfonyl)pyrrolidine-2-carboxylate (I28, 636 mg, 1.1 mmol) in DCM (10 mL) was added TFA (3 mL) at 0° C. The reaction mixture was warmed to room temperature and stirred for 30 min before being concentrated in vacuo. The residue was diluted in DCM (50 mL) and washed with saturated aqueous NaHCO3 (50 mL). The organic phase was passed through a hydrophobic frit and solvent was removed in vacuo. The residue (436 mg) was dissolved in pyridine (4 mL) and the reaction mixture was cooled to 0° C. (R)-quinuclidin-3-yl carbonochloridate hydrochloride (207 mg, 0.92 mmol, prepared as previously reported in 16, step 6) was added and the resulting mixture was stirred at room temperature for 16 h. Additional (R)-quinuclidin-3-yl carbonochloridate hydrochloride (104 mg, 0.46 mmol) was added at 0° C., the mixture was stirred for 2 h and then diluted with EtOAc (50 mL) and water (20 mL). The layers were separated and organic phase dried over MgSO4. The mixture was filtered and the solvent was removed in vacuo to yield 576 mg of the crude title product as a thick oil which was used in the next step without further purification.

Provenance & Evidence