Cyclobutanone → 1-{[6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridin-3-yl](hydroxy)methyl}cyclobutanol

Participants

Reaction Steps

To a solution of 6-(5-{1-[4-(cyclopropylsulfonyl)phenyl]-2-(tetrahydro-2H-pyran-4-yl)ethyl}-1H-pyrrol-2-yl)pyridine-3-carbaldehyde (940 mg) in acetic acid (10 mL) were added cyclobutanone (2.1 g) and 20% aqueous titanium trichloride solution (3.1 g), and the mixture was stirred under argon at room temperature for 16 hr. The reaction mixture was diluted with ethyl acetate, and neutralized with saturated aqueous sodium hydrogen carbonate solution, and filtered through celite to remove the insoluble material. The filtrate was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography to give a pale-yellow amorphous solid from a fraction eluted with ethyl acetate. The obtained pale-yellow amorphous solid was purified by preparative HPLC to give the title compound (75 mg, yield 6.9%) as a colorless amorphous solid. MS: 537 (MH+).

Provenance & Evidence