Hydrochloric Acid → HCID 178448420, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of sodium 5-oxo-5,6-dihydro-2H-pyran-3-olate (Wenke et al. J. Org. Chem. 2006, 71, 1725-1727) (1.36 g, 10.0 mmol) and n-butylthiourea (Trans World) (1.32 g, 10.0 mmol) in tetrahydrofuran (15 mL) was added a mixture of DMSO (2.1 mL) and 12 N HCl (2.5 mL). The reaction mixture was heated at 40° C. overnight and cooled. The mixture was diluted with ethyl acetate and washed with aqueous sodium bicarbonate. The organic extract was dried (MgSO4), filtered and concentrated. The residue was dried under vacuum for 12 hours and dissolved in tetrahydrofuran (40 mL). To the solution was added 5-chloro-2-methoxy-benzoic acid (1.86 g, 10.0 mmol), N-(3-dimethylaminopropyl)-N-ethylcarbodimide hydrochloride (1.91 g, 10.0 mmol), 1-hydroxybenzotriazole (1.35 g, 10.0 mmol) and triethylamine (3.5 mL, 3.5 mmol). The mixture was stirred overnight at 80° C., then cooled to room temperature. The mixture was diluted with ethyl acetate, washed with 1 M aqueous NaHCO3, dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography using an Analogix® IT280™ (SiO2, 0-75% ethyl acetate in hexanes) to afford 412 mg of the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 1.03 (t, J=7.46 Hz, 3H) 1.38-1.52 (m, 2H) 1.77-1.90 (m, 2H) 3.93 (s, 3H) 4.16 (t, J=7.46 Hz, 2H) 4.32 (s, 2H) 4.90 (s, 2H) 6.94 (d, J=8.82 Hz, 1H) 7.40 (dd, J=8.99, 2.88 Hz, 1H) 8.11 (d, J=2.71 Hz, 1H); MS (ESI+) m/z 395 (M+H)+.

Provenance & Evidence