Sulfuryl chloride → 3-Chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester

Participants

Reaction Steps

6-(4-Chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester (16; 483 mg, 1.54 mmol) was slurried in CH2Cl2 (10 mL) and cooled in an ice bath. A solution of SO2Cl2 (209 mg, 1.55 mmol) in CH2Cl2 (5 mL) was added dropwise. After 30 min, the reaction solution was quenched with 10% aqueous sodium bisulfite solution. The organic layer was separated, washed with saturated aqueous NaHCO3 solution, H2O and brine and then dried (MgSO4). The solution was evaporated to a yellow oil which was crystallized from cold methanol to give 3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-4-oxo-1,4,5,6-tetrahydropyridine-2-carboxylic acid methyl ester (33; 0.437 g, 81%) as a light yellow solid: mp 127-129° C.; 1H NMR (300 MHz, CDCl3) δ 7.20 (dd, JF-H=1.5 Hz, JH-H=8.1 Hz, 1H, aromatic), 7.10 (dd, JF-H=6.9 Hz, JH-H=8.1 Hz, 1H, aromatic), 5.82 (br s, 1H, NH), 5.10 (t, J=9.3 Hz, 1H, H6), 3.98 (d, JF-H=1.5 Hz, 3H, OCH3), 3.97 (s, 3H, CO2CH3), 2.88 (d, J=9 Hz, 2H, H5); ESIMS m/z 347.9 ([M+H]+).

Provenance & Evidence