Hydrochloric Acid → 1-[6-(5-{1-[3-Chloro-4-(methylsulfonyl)phenyl]-2-(tetrahydro-2h-pyran-4-yl)ethyl}-1h-pyrrol-2-yl)pyridin-3-yl]ethane-1,2-diol

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-[3-chloro-4-(methylsulfonyl)phenyl]-1-[5-(2,2-dimethyl-1,3-dioxolan-4-yl)pyridin-2-yl]-6-(tetrahydro-2H-pyran-4-yl)hexane-1,4-dione (620 mg) in acetic acid (5 mL) was added ammonium acetate (1.36 g), and the mixture was stirred at 110° C. for 45 min. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate and washed with water. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate and saturated brine, dried (MgSO4) and concentrated to give a crude product (660 mg). To a solution of the obtained crude product (660 mg) in tetrahydrofuran (5 mL) was added 1M hydrochloric acid (5 mL), and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was diluted with ethyl acetate, and washed with saturated aqueous sodium hydrogen carbonate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography, and the title compound (500 mg, yield 90%) was obtained as a pale-yellow amorphous solid from a fraction eluted with ethyl acetate-methanol (9:1, volume ratio). MS: 507 (MH+). 1H NMR (300 MHz, CDCl3) δ1.24-1.48 (3H, m), 1.51-1.62 (3 H, m), 1.74-1.89 (1 H, m), 1.95-2.09 (1H, m), 2.38 (1 H, brs), 3.01 (1 H, s), 3.19-3.34 (5 H, m), 3.55-3.66 (1 H, m), 3.69-3.80 (1 H, m), 3.85-3.97 (2H, m), 4.02-4.14 (1 H, m), 4.78 (1 H, dd, J=7.8, 3.6 Hz), 6.61-6.68 (1 H, m), 7.24 (1 H, dd, J=8.1, 1.7 Hz), 7.32 (1 H, d, J=1.5 Hz), 7.50 (1 H, d, J=8.3 Hz), 7.59-7.67 (1 H, m), 7.97-8.05 (1 H, m), 8.30 (1 H, s), 9.71 (1 H, brs).

Provenance & Evidence